COMPARATIVE STUDY: N-ACETYLCYSTEINE AND METFORMIN ON ATHEROGENIC INDEX IN DIABETIC RATS

Novera Sohail Bajwa, Zoobia Irum, Mehtab Munir, Syed Muzaffar Ali, Mushayada Irshad, Qurra-Tul- Ain Haider

Abstract


Background: Diabetes Mellitus (DM) is a global health issue with severe systemic health effects. A key driver of these complications is prolonged high blood sugar, which enhances the lipolysis and leads to dyslipidemia. Atherogenic index plasma (AIP) significantly heightens the risk of cardiovascular diseases (CVS) in diabetic patients. The objectives of this study were to check the novel use of N- acetylcysteine (NAC) in diabetic rats and to evaluate the comparative effects of NAC and Met on diabetes induced rats.

Materials & Methods: This randomized control trial study was undertaken at the Department of Pharmacology & Therapeutics, Army Medical College Rawalpindi in association with the National Institute of Health (NIH) Islamabad from August 2021 to October 2021. There was a total of twenty-five rats, with five in each group randomized. An intraperitoneal (IP) injection of Streptozotocin (STZ) (35 mg/kg) was given to induce a diabetic condition in the animals. Rats with blood sugar levels in excess of 300 mg/dl after 48 hours were considered to be diabetic. The rats with Diabetes were used as a diabetic control group in one group while the remaining DM rats in three groups were treated with N-acetylcysteine (NAC), Metformin (Met), and Metformin plus N-acetylcysteine (Met + NAC) respectively. The treatment lasted for four weeks. The Atherogenic Index plasma (AIP) of the groups was compared at the end of the trial period. In the statistical analysis, the whole data array was handled with the SPSS 25.0 statistical software package. The Analysis of Variance (ANOVA Test), which compares the variations within all the groups, has been employed, followed by post hoc Tukey test.

Results: There was a total of twenty-five rats, with five in each group randomized. There was a marked improvement in the Atherogenic index plasma (AIP) for the N-acetylcysteine (NAC) group, as well as for the Metformin + N- acetylcysteine (Met + NAC) group having a p value <0.001in these groups.

Conclusion: The use of antioxidants, including N-acetylcysteine, caused a significant decrease in the Atherogenic Index Plasma in a diabetes-induced model produced by Streptozotocin.


Keywords


Atherogenic Index Plasma; Cardiovascular Diseases; Dyslipidemias; Hyperglycemia; Metformin; N-acetylcysteine; Streptozotocin.

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References


Al-Shaer MH, Elzaky MM, Farag ESM, Saad MOM. Atherogenic index of plasma as a marker of coronary artery disease in type 2 diabetes mellitus patients. Indian J Clin Cardiol. 2021;2(4):217-221. https://doi.org/10.1177/26324636211031362

Tenório MCS, Graciliano NG, Moura FA, Oliveira ACM, Goulart MOF. N-acetylcysteine (NAC): impacts on human health. Antioxidants (Basel). 2021;10(6):967. https://doi.org/10.3390/antiox10060967

Fu L, Zhou Y, Sun J, Zhu Z, Xing Z, Zhou S, et al. Atherogenic index of plasma and major adverse cardiovascular events in patients with type 2 diabetes mellitus. Cardiovasc Diabetol. 2021;20:1-11. https://doi.org/10.1186/s12933-021-01393-5

Domínguez MAM, González MLZ, Muñiz ERZ, Varela VAM, Nájera CAI, Robledo NSF, et al. Inflammation and atherogenic markers in type 2 diabetes mellitus. Clin Investig Arterioscler (Engl Ed). 2022;34(3):105-112. https://doi.org/10.1177/00033197211012129

Zhou K, Qin Z, Tian J, Cui K, Yan Y, Lyu S. Atherogenic index of plasma as a predictor for coronary artery disease in type 2 diabetes patients. Angiology. 2021;72(10):934-941.

Kalamkar S, Acharya J, Kolappurath Madathil A, Gajjar V, Divate U, Karandikar-Iyer S, et al. Long-term glutathione supplementation improves oxidative damage and HbA1c in elderly type 2 diabetic patients: a randomized clinical trial. Antioxidants (Basel). 2022;11(5):1026. https://doi.org/10.3390/antiox11051026

Johnson R, Sangweni NF, Mabhida SE, Dludla PV, Mabasa L, Riedel S, et al. Combination effect of metformin and N-acetylcysteine against hyperglycaemia-induced cardiac damage: an in vitro study. Nutrients. 2019;11(12):2850. https://doi.org/10.3390/nu11122850

Poznyak AV, Litvinova L, Poggio P, Moschetta D, Sukhorukov VN, Orekhov AN. From diabetes to atherosclerosis: potential of metformin for cardiovascular disease management. Curr Pharm Des. 2022;28(16):1324-1336. https://doi.org/10.2174/1381612828666220310142620

Kheniser KG, Kashyap SR, Kasumov T. Effects of metformin on lipoprotein modification and function: a systematic review. Obes Sci Pract. 2019;5:36-45. https://doi.org/10.1002/osp4.323

Sundararajan S, Jayachandran I, Pandey GK, Venkatesan S, Rajagopal A, Gokulakrishnan K, et al. Metformin reduces atherogenesis via the Sestrin2-mTOR pathway in obese and diabetic rats. J Lipid Atheroscler. 2023;12(3):290-306. https://doi.org/10.12997/jla.2023.12.3.290

Li M, Hu X, Xu Y, Hu X, Zhang C, Pang S. A possible mechanism of metformin in improving insulin resistance in diabetic rat models. Int J Endocrinol. 2019;2019:3248527. https://doi.org/10.1155/2019/3248527

Rosa LR, Kaga AK, Barbanera PO, Queiroz PM, do Carmo NO, Fernandes AA. Beneficial effects of N-acetylcysteine on hepatic oxidative stress in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol. 2018;96(4):412-418. https://doi.org/10.1139/cjpp-2017-0598

Shen X, Wang L, Zhou N, Gai S, Liu X, Zhang S. Beneficial effects of combination therapy of phloretin and metformin in streptozotocin-induced diabetic rats and improved insulin sensitivity in vitro. Food Funct. 2020;11(1):392-403. https://doi.org/10.1039/c9fo01912b

Xu J, Zhou H, Xiang G. Association of atherogenic index of plasma with retinopathy and nephropathy in adult patients with type 2 diabetes mellitus aged> 18 years. Canadian journal of diabetes. 2022 Oct 1;46(7):708-14. https://doi.org/10.1016/j.jcjd.2022.03.006

Al-Nami MS, Al-Kuraishy HM, Al-Gareeb AI. Thioctic acid effects on glycemic indices and endothelial dysfunction in type 2 diabetes mellitus. Int J Crit Illn Inj Sci. 2020;10(Suppl 1):21-27. https://doi.org/10.4103/IJCIIS.IJCIIS_80_19

Sun M, Lu Z, Chen WM, Lv S, Fu N, Yang Yet al. N-acetylcysteine therapy reduces major adverse cardiovascular events in patients with type 2 diabetes mellitus. Atherosclerosis. 2025 Mar 1;402:119117. https://doi.org/10.1016/j.atherosclerosis.2025.119117

Abdel-Moneim AM, Lutfi MF, Alsharidah AS, Shaker G, Faisal Wet al. Short-term treatment of metformin and glipizide on oxidative stress, lipid profile and renal function in a rat model with diabetes mellitus. Applied Sciences. 2022 Feb 15;12(4):2019. https://doi.org/10.3390/app12042019

Li X, Zou J, Lin A, Chi J, Hao H, Chen H, Liu Z. Oxidative stress, endothelial dysfunction, and N-acetylcysteine in type 2 diabetes mellitus. Antioxidants & Redox Signaling. 2024 Jun 1;40(16-18):968-89. https://doi.org/10.1089/ars.2023.0278

Ghasemi-Dehnoo M, Amini-Khoei H, Lorigooini Z, Rafieian-Kopaei M. Oxidative stress and antioxidants in diabetes mellitus. Asian Pac J Trop Med. 2020;13(10):431-438. https://doi.org/10.4103/1995-7645.288651

Naz R, Saqib F, Awadallah S, Wahid M, Latif MF, Iqbal I, et al. Food polyphenols and type II diabetes mellitus: mechanisms and pharmacology. Molecules. 2023;28(10):3996. https://doi.org/10.3390/molecules28103996

Xing S, Guo Z, Lang J, Zhou M, Cao J, He H et al. N-Acetyl-l-cysteine ameliorates gestational diabetes mellitus by inhibiting oxidative stress. Gynecological Endocrinology. 2023 Dec 14;39(1):2189969. https://doi.org/10.1080/09513590.2023.2189969

Cui M, Xiao X, Zhao X, Wang Y, Gang X, Wang G. Association between the atherogenic index of plasma and chronic kidney disease: an evaluation of an adult population of American patients with diabetes mellitus. Renal Failure. 2025 Dec 31;47(1):2556495. https://doi.org/10.1080/0886022X.2025.2556495

Blahova J, Martiniakova M, Babikova M, Kovacova V, Mondockova V, Omelka R. Pharmaceutical and natural products for treatment of type 2 diabetes mellitus. Pharmaceuticals (Basel). 2021;14(8):806. https://doi.org/10.3390/ph14080806

Panahi Y, Ostadmohammadi V, Raygan F, Sharif MR, Sahebkar A. The effects of N-acetylcysteine administration on metabolic status and serum adiponectin levels in patients with metabolic syndrome: A randomized, double-blind, placebo-controlled trial. Journal of Functional Foods. 2022 Dec 1;99:105299. https://doi.org/10.1016/j.jff.2022.105299




DOI: https://doi.org/10.46903/gjms/24.1.2267

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