{"id":54602,"date":"2023-12-31T10:50:04","date_gmt":"2023-12-31T10:50:04","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=54602"},"modified":"2024-01-05T06:46:39","modified_gmt":"2024-01-05T06:46:39","slug":"assessment-of-il-6-mda-gsh-and-serum-electrolytes-in-diabetic-patients","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no4\/assessment-of-il-6-mda-gsh-and-serum-electrolytes-in-diabetic-patients\/","title":{"rendered":"Assessment of IL-6, MDA, GSH and Serum Electrolytes in Diabetic Patients"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

The metabolic syndrome recognized as diabetes mellitus (DM) has been receiving a lot of attention from the public health community. It is characterized by an uncontrolled elevation of blood sugar (hyperglycemia) as a result of insulin deficiency caused by pancreatic beta cell damage or decreased (insulin release)or by the (bodykcell’s) inabilitya such as musclesk to detect and utilize the circulating insulin, a condition known as(insulin sensitivity) or (IR Insulin Resistance)1,2,3<\/sup>.<\/p>\n\n\n\n

The primary kinds of diabetes are (diabetes mellitus type 2 T2DM), which is primarily carried on by tissue resistance to circulation insulin present in the blood, and  (diabetes mellitus type 1 T1DM), an auto-immune disease characterized via the indiscriminate death of -pancreatic beta cells4<\/sup>. Individuals with diabetes mellitus are susceptible to severe consequences from associated conditions such as hypertension, hyperlipidemiaa, nneuropathy, kobesity, chronics kidney disease(CKD), and cardiovascularj disease (CVD) 5<\/sup>. Among the detrimental consequences of diabetes on the bodyh systems that are currently hgaining substantial attention in the fields of publickhealth and medicalyresearch are a number of diabetic illnesses, including diabetic retinopathy, neuropathy, and nephropathy. Meanwhile, it’s also noteworthy that patients with diabetes who also have kidney, nerve, and vascular issues frequently experience similar diseases 6,7<\/sup>.<\/p>\n\n\n\n

Interleukin-6g(IL-6)<\/strong><\/p>\n\n\n\n

Interleukin-6g(IL-6) functions as an activating cytokine to regulate insulin output. Insulin is one of the most important hormones for regulating the amount of glucose in the body. Its effects are influenced by secretion, cellular sensitivity, and clearing. Numerous studies have examined how IL-6 affects insulin secretion and levels 8<\/sup>. Due to its direct or indirect effects on insulin release through the increase of excess lipid production and glucose homeostasis, interleukin-6 functions as an inflammatory marker. Furthermore, it’s possible that the IL-6 gene contributes to T1DM susceptibility 9<\/sup>.<\/p>\n\n\n\n

Moreover, IL-6 may actually harm pancreatic cells by promoting the growth of B lymphocytes and triggering killer T cells. Inflammation-mediating cytokines, such as TNF-alfa and IL-1,which are produced from macrophages and trigger the production of IL-6 as a consequence of many biological processes, are crucial for the onset of type 1 diabetes 10<\/sup>. By functioning as an activating cytokine, interleukin-6 regulates insulin secretion. Previous research has shown that low concentrations of IL-6 can increase insulin release, whereas high amounts reduce insulin synthesis. Additionally, the vulnerability to T2DM may be influenced by the IL-6 gene 11<\/sup>. Since IL-6 can communicate through both liquid (trans-signaling) and cell wall-attached (cis-signaling) IL-6 sensors, it affects inflammatory, immunological, and diverse cells, including fat, skeletal muscle, and pancreatic cells. Elevated IL-6 levels have a substantial impact on diabetes risk, and either by itself or in combination with IL-1\u03b2 30, this cytokine inhibits \u03b2 cell function 12<\/sup>.<\/p>\n\n\n\n

Oxidative stress (OS) <\/strong><\/p>\n\n\n\n

Oxidative stress is a major cause of diabetic mellitus. The body produces a few toxic RNS and ROS under normal physiological settings, and its antioxidant defense eliminates both of them quickly beforenthey cause anygstructural or functionaljdamage. This delicate balance, however, means that cellular damage caused by ROS and RNS occurs often. As a result, damaged molecules need to be replaced or repaired, as shown in vivo in humans and animals 13<\/sup>.    <\/p>\n\n\n\n

The\namount of cellular antioxidant-oxidant balance is compromised by oxidative\nstress, which increases the buildup of dangerous free radicals and lipid\nperoxidation byproducts that distort cellular functions and collaborate well\nwith increased inflammatory activities frequently seen in diabetic patients 14<\/sup>. The\neffects of the condition, including vascular integrity impairment, polydipsia,\nfrequent urination, hyperglycemia, and nervous system dysfunction, may be\nsignificantly impacted. In DM, there are more free radicals or less antioxidant\nactivity 15<\/sup>. While\nsevere exposure to oxidants results in disrupted chemical signaling and\npossibly damage to biomolecules, low exposure causes redox alterations in the\nparticular target molecules that contribute to redox signaling (oxidative\neustress). These pathways are modulated and counteracted by adaptive responses.\nIt either promotes the advancement of health or sickness, depending on the\nresult 16<\/sup>.<\/p>\n\n\n\n

The\nmitochondrial electron transport chain produces more ROS when blood glucose\nlevels are elevated in diabetic patients. Moreover, the high reactivity of ROS\ncauses chemical alterations in almost every component of the cell, including\nlipid peroxidation, DNA and protein modification, and other processes that contribute-to-the\ndevelopment of diabetic-nephropathy(DN). Since\nthe imbalance among these two categories of particles with respect to the\npro-oxidant agents causes oxidative stress, there is a significant need in\nmedical and scientific fields for accurate and efficient methods in performing\na quantitative evaluation of oxidative damage in biological samples, followed\nby the detection of ROS\/RNS and antioxidants. Therefore, research in the\nbiological and pharmaceutical domains, with a focus on DM, greatly benefits\nfrom the development of novel ROS\/RNS or antioxidant testing techniques 17<\/sup>.<\/p>\n\n\n\n

Additionally,\nit is critical to evaluate these species in various cellular contexts and\nprovide insight into the ensuing pathomechanisms that support the onset and\nadvancement of DM-associated DN.<\/p>\n\n\n\n

Antioxidants<\/strong><\/p>\n\n\n\n

On the opposite part of the redox equilibrium, antioxidants have conflicting effects on RNS and ROS. Antioxidants are described as organisms that lessen oxidative stress through the suppression of radical chain reactions inside carbohydrates, lipids, proteins, or DNA, or the degradation of ROS\/RNS to reduce reactive species. An organism contains a wide range of active endogenous and exogenous antioxidants. They fall into two categories: non-enzymatic (partially supplied by food intake) and enzymatic (endogenous). The production of low molecular weight moleculesk(e.g.,bglutathione, GSH, or bilirubin)and endogenous antioxidantoenzymes (e.g., superoxide dismutase,iSOD)or both directly correlates with the functioning of the antioxidant system and can be enhanced by physical activity, dietary enrichment, or fasting for an extended period 18<\/sup>.<\/p>\n\n\n\n

Glutathione<\/strong><\/p>\n\n\n\n

Glutathione is a sulfur-based organic compound identified by the sulfhydryl residues (-SH) in their active sites. Cysteine, which can be readily oxidized, is the main thiol material in the body. A cysteine residue’s-oxidation can alter a protein’s functionality. As a result, thiolastatus measurement could be useful as a mechanismhbased marker. Protein thiols and lowcmolecularkweight thiols like cysteine and GSH are examples of thiolsa found in biological systems. The kind of reactive species active in the oxidative alteration, the electrochemical environmentg(pH and cofactor availability) and chemicalbredox thehstate, the pKa-value, and the structural-microenvironment of the targeted-thiol all influence the utilization of thiols as biomarkers 19<\/sup>. Apart from the particular constraints pertaining to thiols, which are exclusively found within cells, the overarching issue is the instability of the oxidation products resulting from protein cysteine residues, necessitating rapid assessment. They can be rapidly reduced by other thiols, thus it’s imperative to treatdthem right away with anvalkylating substance to stop more redoxcchanges. Another drawback of this approach is that variations in GSH levels may not always be the result of oxidativebstress but also indicate a nutritional, or metabolicvimbalance. GSH transporters may also have an impact on plasma GSH levels, however, Nrf2 cellular mechanisms increase GSH production in response to oxidative stress. Lastly, unless sophisticated HPLC techniques are employed, GSSG quantities are tiny and challenging to assess 20<\/sup>. The latter may be used as a possible diagnostic tool, for example, to quantify the GSH and GSSG ratio from patient plasma using an advanced HPLC approach. Scientists began using this method on patients in 1989. The activity of glutathione synthetase and y-glutamylcysteine synthetase in the erythrocytes of patients with T2DM was assessed using a basic enzymatic technique. These patients showed a reduction in the GSH\/GSSG ratio. Glutathione metabolite measurement provides unique information about the redox state 21,22<\/sup>.<\/p>\n\n\n\n

This study aims\nto evaluate the levels of interleukin-6 in patients with type 2 diabetes, which\nis considered a good indicator of the occurrence of chronic inflammation, which\nin turn can generate many free radicals that doing lipids peroxidation of cell\nmembranes and fatty acids present in the blood, which are estimated by the MDA.\nIn addition to estimating the level of glutathione, which expresses the\nstrength of antioxidants in the body. As a result of some imbalances in\nelectrolyte concentrations in diabetic patients, they were measured compared to\nhealthy people.<\/p>\n\n\n\n

Materials and Method<\/strong><\/p>\n\n\n\n

Sample Collection<\/strong><\/p>\n\n\n\n

Blood serum samples for patients with type 2 diabetes were collected from Marjan Medical City in Babylon Governorate (from December 2022 to April 2023), after obtaining ethical medical approvals from the Babylon Health Department. Patients who are diagnosed with type 2 diabetes by specialized doctors in addition to their medical history. 5 ml of patients’ blood samples were drawn after a period of fasting (8-12) hours, and samples were drawn from a group of healthy people similar to them in terms of age and gender, which numbered 100 men and 100 women (total samples equal to 200). Excluded criteria: All patients with diabetic nephropathy, cardiovascular disease, pulmonary disease, chronic diseases other than diabetes, and autoimmune diseases such as rheumatoid arthritis were excluded.<\/p>\n\n\n\n

Estimation of the level of lipid peroxidation<\/strong><\/p>\n\n\n\n

In diabetic patients and healthy control, lipids peroxidation has been measured. This assay was done through the reaction of malondialdehyde (MDA) with thiobarbituric acid (TBARS) in acidic medium 23<\/sup>.<\/p>\n\n\n\n

Estimation of the level of reduced glutathione (GSH)<\/strong><\/p>\n\n\n\n

Reduced glutathione (GSH) assay levels in the serum was performed. TCA (400 \u00b5L; 20%) and a 100 \u00b5L sample of serum were combined, and the mixture was then centrifuged one more (10 minte, 4 \u00b0C, 10,000 rpm). The supernatants (2.5 mL) centrifuged, then add to (DTNB 2mL;0.6M), and then incubation for10 min at room temperature. At (412 nm absorbance) was finally measured 24<\/sup>.<\/p>\n\n\n\n

Estimation of IL-6 by ELISA<\/strong><\/p>\n\n\n\n

Quantified IL-6 in patient serum at room temperature in accordance with instructions from the ELISA kit’s manufacturer. The samples’ levels of IL-6 were measured, computed using the kits’ standard curve, and expressed in (pg\/mL).<\/p>\n\n\n\n

Serum Electrolyte Level Estimations<\/strong><\/p>\n\n\n\n

Sodium, potassium, and calcium  were all estimated in the serum using the appropriate commercial kits. Spectrophotometric methods were used in all electrolyte measurements.<\/p>\n\n\n\n

Analytical Statistics<\/strong><\/p>\n\n\n\n

(Analysis\nof varianceANOVA)was used to analyze the data,followed by the Tukey post hoc\ntest to compared results across all experimentala groups and the results were given as Means\nSEM. At p 0.05, all statistical differences were deemed significant.<\/p>\n\n\n\n

Results and Discussion<\/strong><\/p>\n\n\n\n

Table\n1 of the results for age and BMI, as well as the duration of diabetes for\npatients compared to healthy people.<\/p>\n\n\n\n

Table 1: The Results of Demographic Study.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Parameters<\/strong><\/p>\n<\/td>\n

\n

Groups<\/strong><\/p>\n<\/td>\n

\n

Means \u00b1 SD<\/strong><\/p>\n<\/td>\n

\n

95%(Confidence Intervals)<\/strong><\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

P-Value<\/strong><\/p>\n

 <\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Lower<\/strong><\/p>\n<\/td>\n

\n

Upper<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Age\/Years<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

50.37\u00b110.05<\/p>\n<\/td>\n

\n

45.64<\/p>\n<\/td>\n

\n

60.16<\/p>\n<\/td>\n

\n

0.15<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

52.24\u00b18.34<\/p>\n<\/td>\n

\n

46.17<\/p>\n<\/td>\n

\n

61.90<\/p>\n<\/td>\n<\/tr>\n

\n

BMI<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

23.65\u00b12.19<\/p>\n<\/td>\n

\n

21.88<\/p>\n<\/td>\n

\n

24.19<\/p>\n<\/td>\n

\n

0.094<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

21.47\u00b10.39<\/p>\n<\/td>\n

\n

20.13<\/p>\n<\/td>\n

\n

22.12<\/p>\n<\/td>\n<\/tr>\n

\n

   Duration\/Years<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

10.08\u00b13.00<\/p>\n<\/td>\n

\n

6.30<\/p>\n<\/td>\n

\n

13.18<\/p>\n<\/td>\n

\n

NF<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

_<\/p>\n<\/td>\n

\n

_<\/p>\n<\/td>\n

\n

_<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

NF: Not Found<\/p>\n\n\n

The samples were taken on the basis of the great similarity between patients and healthy people in terms of age and BMI, so there is no significant difference between them and the reason is to reduce some physiological differences between people. The duration of the disease was also taken into account from the beginning of diabetes until the samples were collected, in order to demonstrate the complications of diabetes in patients and their effect on their levels of oxidation – antioxidants. Long periods of illness, especially for patients with uncontrolled diabetes, may have a negative impact on kidney functions, which was assessed through the electrolyte values mentioned in Table 2.<\/p>\n\n\n\n

Table 2: The Results of Biochemical Parameters.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Parameters<\/strong><\/p>\n<\/td>\n

\n

Groups<\/strong><\/p>\n<\/td>\n

\n

Means \u00b1 SD<\/strong><\/p>\n<\/td>\n

\n

95%(Confidence Intervals)<\/strong><\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n

P-Value<\/strong><\/p>\n

 <\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Lower<\/strong><\/p>\n<\/td>\n

\n

Upper<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Fasting Blood Glucose (mg\/dL)<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

265\u00b121<\/p>\n<\/td>\n

\n

240<\/p>\n<\/td>\n

\n

280<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

86\u00b17<\/p>\n<\/td>\n

\n

78<\/p>\n<\/td>\n

\n

90<\/p>\n<\/td>\n<\/tr>\n

\n

HbA1C%<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

12.8\u00b13.4<\/p>\n<\/td>\n

\n

9.44<\/p>\n<\/td>\n

\n

14.32<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

4.23\u00b11.15<\/p>\n<\/td>\n

\n

4.01<\/p>\n<\/td>\n

\n

5.09<\/p>\n<\/td>\n<\/tr>\n

\n

IL-6 (Pg\/mL)<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

215\u00b131<\/p>\n<\/td>\n

\n

187<\/p>\n<\/td>\n

\n

244<\/p>\n<\/td>\n

\n

<0.001<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

52\u00b110<\/p>\n<\/td>\n

\n

43<\/p>\n<\/td>\n

\n

60<\/p>\n<\/td>\n<\/tr>\n

\n

MDA (\u00b5mol\/L)<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

3.19\u00b1 0.77<\/p>\n<\/td>\n

\n

3.65<\/p>\n<\/td>\n

\n

4.11<\/p>\n<\/td>\n

\n

0.021<\/p>\n<\/td>\n<\/tr>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

8.42 \u00b1 0.75<\/p>\n<\/td>\n

\n

8.03<\/p>\n<\/td>\n

\n

8.93<\/p>\n<\/td>\n<\/tr>\n

\n

GSH (mmol\/L)<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

30.07\u00b14.86<\/p>\n<\/td>\n

\n

26.05<\/p>\n<\/td>\n

\n

33.14<\/p>\n<\/td>\n

\n

0.013<\/p>\n<\/td>\n<\/tr>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

20.01\u00b1 3.25<\/p>\n<\/td>\n

\n

18.11<\/p>\n<\/td>\n

\n

22.53<\/p>\n<\/td>\n<\/tr>\n

\n

S. Na+<\/sup> (mg\/dL)<\/strong><\/p>\n<\/td>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

155\u00b18.04<\/p>\n<\/td>\n

\n

149<\/p>\n<\/td>\n

\n

161<\/p>\n<\/td>\n

\n

0.078<\/p>\n<\/td>\n<\/tr>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

147\u00b15.11<\/p>\n<\/td>\n

\n

145<\/p>\n<\/td>\n

\n

151<\/p>\n<\/td>\n<\/tr>\n

\n

S. K+<\/sup> (mmol\/L)<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

4.41\u00b10.37<\/p>\n<\/td>\n

\n

4.21<\/p>\n<\/td>\n

\n

4.63<\/p>\n<\/td>\n

\n

0.016<\/p>\n<\/td>\n<\/tr>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

6.7\u00b10.59<\/p>\n<\/td>\n

\n

5.98<\/p>\n<\/td>\n

\n

6.95<\/p>\n<\/td>\n<\/tr>\n

\n

S. Ca2+<\/sup> (mg\/dL)<\/strong><\/p>\n<\/td>\n

\n

Control<\/strong><\/p>\n<\/td>\n

\n

9.41\u00b10.61<\/p>\n<\/td>\n

\n

8.79<\/p>\n<\/td>\n

\n

10.02<\/p>\n<\/td>\n

\n

0.81<\/p>\n<\/td>\n<\/tr>\n

\n

Patients<\/strong><\/p>\n<\/td>\n

\n

8.93\u00b10.77<\/p>\n<\/td>\n

\n

8.36<\/p>\n<\/td>\n

\n

9.72<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n\n\n

The high blood sugar values in patients (265\u00b121), as well as the significant difference in the high glycated hemoglobin in patients (12.8\u00b13.4) compared to healthy people (86\u00b17) and (4.23\u00b11.15), respectively, indicate the type of diabetes in patients is the  uncontrolled type 2 DM and causes many complications. The most prominent complications of diabetes are (high blood pressure, nerve cell dysfunction, oobesity, nephropathy, yretinopathy, and cardiovascularjdisease). An imbalance in the state of oxidation and antioxidants also plays a rolef in the emergences and progression of a number of pathologicalf conditions 25<\/sup>. These comorbidities frequently induce (OS-oxidative stress)and also an inflammatory responses, indicating the oxido-inflammatory activity may be the root of the diseases. Cell structure is impacted by free radical accumulation and diminished antioxidant activity, which amplifies the production of transcriptional regulators and proteins, which forces changes in cellular processes and stimulates inflammatory response and apoptosis 26<\/sup>.<\/p>\n\n\n\n

Diabetes\nmellitus was associated in this study by along with a rise in oxidant and\ndecrease in antioxidant increase of cytokines that are pro-inflammatory. According\nto the study’s findings, the induction of diabetes mellitus causes metabolic\nimbalance by upregulating the oxidoonitrosative (pro-oxidants release), and inflammatoryd condition in the kidney,\nand brain ccells.\nThis, in turn, causes neuronal cell and kidney damage. By damaging structural\nelements, the creation of these free radicals may seriously affect renal\nfunction. The circumstance may provide an environment that mobilizes and\nencourages the development of transcription factors that represent diabetic\nnephropathy and proinflammatory cytokinesg(such vTNF-\u03b1\nand jIL-6). In a\nrelated study on diabetic and kidney diseases, it was shown that\ndiabetes-induced oxidative stress, which is linked to abnormalities in kidney\nfunction, is a primary suspectf\nfor cellulard damaged\nand the developmentk\nof diabeticdkidneyhdisease,or diabetic nephron-pathy\nby elevated IL-6 and TNF-\u03b1 that associated with disturbance of kidney functions 27<\/sup>.<\/p>\n\n\n\n

Through\nthe elevations in the level of HbA1C for uncontrolled diabetics lead to\ndisturbances in their levels of electrolytes were observed, through a\nsignificant increase in potassium levels (hyperkalemia) which as a result\ncauses metabolic acidosis, which in turn increases the incidence of\ninflammation and thus a rise in interleukin-6 levels. It is necessary to follow\nthe values of the glycated hemoglobin (HbA1C) levels in patients to assess\ntheir health conditions and their response to medications in order to reduce\ncomplications resulting from the development of the disease with a healthy diet\nand good diet as well as exercise to reduce oxidative stress.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

It\nis concluded from the study that high levels of glycated hemoglobin are a state\nof uncontrolled diabetes that causes many problems, including the occurrence of\nlow-grade inflammation, which is determined by high levels of interleukin 6,\nwhich in turn increases the rise of free radicals and raises levels of lipid\nperoxidation. In contrast, levels of total antioxidants, represented here by\nglutathione, decrease. Disturbances in the levels of electrolytes in the blood,\nincluding high levels of potassium, and thus the occurrence of metabolic\nacidosis, resulting from the beginning of kidney deterioration in patients with\nuncontrolled diabetes or maybe the result of a difference in the acid-base\nbalance within the body resulting from an increase in ketone bodies.<\/p>\n\n\n\n

Acknowledgment<\/strong><\/p>\n\n\n\n

We extend my thanks and appreciation to the medical staff of (Marjan Teaching Hospital) for their assistance in completing the researches.<\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

There is no conflict with others.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

There are no sources of funding.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. Khan M, Shah MA, Kamal M, Ola MS, Ali M, Panichayupakaranant P. Comparative antihyperglycemic and antihyperlipidemic effects of lawsone methyl ether and lawsone in nicotinamide-streptozotocin-induced diabetic rats. Metabolites<\/em>. 2023;13(7):863.
    CrossRef<\/a><\/li>
  2. Ajirioghene AE, Ghasi SI, Ewhre LO, Adebayo OG, Asiwe JN. Anti-diabetogenic and in vivo antioxidant activity of ethanol extract of Dryopteris dilatata in alloxan-induced male Wistar rats. Biomarkers<\/em>. 2021;26(8):718-725.
     CrossRef <\/a><\/li>
  3. Akpotu AE, Asiwe JN, Ikponmwosa A, Abeje JI, Eruotor HO, Adebayo OG. Dryopteris dilatata extract alleviates neuronal derangements and kidney disturbances in streptozotocin-induced diabetic nephropathy via concomitant activation of Nrf2\/Bcl-2\/antioxidants axis. Phytomedicine Plus<\/em>. Published online 2022:100363.
     CrossRef <\/a><\/li>
  4. Vila\u00e7a Pereira de Ara\u00fajo Pizarro \u00c2M, Martins MRO, Almeida Sim\u00f5es J. Exploring the Policies Applied to Pharmaceutical Care Practice for Type 2 Diabetes over the Last Decade in European Community Pharmacies. Rev Port Sa\u00fade P\u00fablica\/Portuguese J Public Heal<\/em>. 2021;39(2).
     CrossRef <\/a><\/li>
  5. Touyz RM, Eluwole O, Camargo LL, et al. Molecular Mechanisms Underlying Vascular Disease in Diabetes. In: Blood Pressure Disorders in Diabetes Mellitus<\/em>. Springer; 2023:105-118.
    CrossRef <\/a><\/li>
  6. Rajendiran D, Packirisamy S, Joy P, Raghavan S. Antidiabetic potential of Indian medicinal plants-A review.<\/li>
  7. Muthuraman N, Vijayselvi R, Christudoss P, Abraham P. Assessment of serum biotin levels and its association with blood glucose in gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol X<\/em>. 2023;17:100181.
     CrossRef <\/a><\/li>
  8. Mustika A, Fatimah N, Safitri I, Susanti N, Noor NS. Clinacanthus nutans L Extracts Reduce the Serum Tumor Necrosis Factor-\u03b1, Malondialdehyde, and Interleukin-6 Levels and Improve the Langerhans Islet Area in Diabetic Rat Models. Clin Med Insights Endocrinol Diabetes<\/em>. 2023;16:11795514231196462.
     CrossRef <\/a><\/li>
  9. Maqsood M, Sharif S, Naz S, et al. Expression of pro-inflammatory cytokines (IL-6 & IL-18) exacerbate the risk of diabetic nephropathy in the Pakistani population. Mol Biol Rep<\/em>. 2023;50(4):3249-3257.
     CrossRef <\/a><\/li>
  10. Miller AH, Binder EB. Guilt by association: inflammation and shared genetic risk between stress-related and immune disorders. Am J Psychiatry<\/em>. 2023;180(4):259-261.
     CrossRef <\/a><\/li>
  11. Kullenberg H, Nystr\u00f6m T, Kumlin M, Svedberg MM. Correlation between insulin-degrading enzyme versus total tau and selected cytokines in patients with Alzheimers disease compared to non-demented controls. Neuroendocrinol Lett<\/em>. 2023;44(4).<\/li>
  12. Pestana RMC, Domingueti CP, Duarte RCF, et al. Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy. Immunol Res<\/em>. 2016;64:951-960.
    CrossRef <\/a><\/li>
  13. Zhu L, Luo M, Zhang Y, et al. Free radical as a double-edged sword in disease: Deriving strategic opportunities for nanotherapeutics. Coord Chem Rev<\/em>. 2023;475:214875.
     CrossRef <\/a><\/li>
  14. Rajlic S, Treede H, M\u00fcnzel T, Daiber A, Duerr GD. Early detection is the best prevention\u2014Characterization of oxidative stress in diabetes mellitus and its consequences on the cardiovascular system. Cells<\/em>. 2023;12(4):583.
     CrossRef <\/a><\/li>
  15. Caturano A, D\u2019Angelo M, Mormone A, et al. Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Curr Issues Mol Biol<\/em>. 2023;45(8):6651-6666.
    CrossRef <\/a><\/li>
  16. An Y, Xu B tuo, Wan S rong, et al. The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction. Cardiovasc Diabetol<\/em>. 2023;22(1):237.
     CrossRef <\/a><\/li>
  17. Mukai E, Fujimoto S, Inagaki N. Role of reactive oxygen species in glucose metabolism disorder in diabetic pancreatic \u03b2-cells. Biomolecules<\/em>. 2022;12(9):1228.
     CrossRef <\/a><\/li>
  18. Nwozo OS, Effiong EM, Aja PM, Awuchi CG. Antioxidant, phytochemical, and therapeutic properties of medicinal plants: A review. Int J Food Prop<\/em>. 2023;26(1):359-388.
     CrossRef <\/a><\/li>
  19. Bayram I, Decker EA. Underlying mechanisms of synergistic antioxidant interactions during lipid oxidation. Trends Food Sci Technol<\/em>. Published online 2023.
    CrossRef <\/a><\/li>
  20. Zhang Y, Li Y, Ren X, Zhang X, Wu Z, Liu L. The positive correlation of antioxidant activity and prebiotic effect about oat phenolic compounds. Food Chem<\/em>. 2023;402:134231.
     CrossRef <\/a><\/li>
  21. Lu X, Gu X, Shi Y. A review on lignin antioxidants: Their sources, isolations, antioxidant activities and various applications. Int J Biol Macromol<\/em>. 2022;210:716-741.
    CrossRef <\/a><\/li>
  22. Martemucci G, Costagliola C, Mariano M, D\u2019andrea L, Napolitano P, D\u2019Alessandro AG. Free radical properties, source and targets, antioxidant consumption and health. Oxygen<\/em>. 2022;2(2):48-78.
     CrossRef <\/a><\/li>
  23. Lu Y, Wan S, Ruan X, et al. Phosphoric acid induced controllable nanoparticle aggregation for ultrasensitive SERS detection of malondialdehyde in a microfluidic chip. Chemosensors<\/em>. 2022;10(12):524.
     CrossRef <\/a><\/li>
  24. Zhang H, Wu S, Xing Z, Wang J, Wang HB, Fang L. Sensitive Fluorescent Determination of Silver Ion and Glutathione in Human Serum Using Polydopamine Nanodots as the Probe. Anal Lett<\/em>. Published online 2023:1-12.
     CrossRef <\/a><\/li>
  25. Ergashev UY, Zokhirov AR, Minavarkhujaev RR. Study and treatment of changes in biochemical processes in complications of diabetes mellitus. Published online 2023.<\/li>
  26. Galiero R, Caturano A, Vetrano E, et al. Peripheral neuropathy in diabetes mellitus: Pathogenetic mechanisms and diagnostic options. Int J Mol Sci<\/em>. 2023;24(4):3554.
     CrossRef <\/a><\/li>
  27. Li X, Huang Y, Liu Y, et al. Circulating VEGF-A, TNF-\u03b1, CCL2, IL-6, and IFN-\u03b3 as biomarkers of cancer in cancer-associated anti-TIF1-\u03b3 antibody-positive dermatomyositis. Clin Rheumatol<\/em>. 2023;42(3):817-830.
     CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

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