Nephroprotective Effect of Coenzyme Q10 alone and in Combination with N-acetylcysteine in Diabetic Nephropathy

European Pharmaceutical Journal Pub Date : 2021-01-01 DOI:10.2478/afpuc-2020-0020

Manoj Mahajan, A. Upaganlawar, Chandrashekar D. Upasani

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Abstract

Abstract Aim Oxidative stress due to chronic hyperglycaemia is a key factor in the development and progression of various microvascular complications including diabetic nephropathy (DN) and associated renal injury. Treatment with antioxidants is one of the strategies to protect the kidney from oxidative tissue damage to improve renal physiology during DN. The investigation, therefore, was designed to assess the nephroprotective effect of coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), either alone or in combination in streptozotocin (STZ)-nicotinamide (NAD) induced diabetic nephropathy (DN) in rats. Methods T2DM induced by STZ (55 mg/kg, i.p.)-NAD (110 mg/kg, i.p.) in Sprague-Dawley rats (220–250 g) was confirmed by the elevated blood glucose level and glycated haemoglobin. DN was assessed by renal function tests. The diabetic rats were treated with CoQ10 (10 mg/kg, p.o.) and/or NAC (300 mg/kg, p.o.) for 8 weeks after confirmation of DN. Oxidative tissue damage due to STZ-NAD was estimated by malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT), reduced glutathione (GSH), myeloperoxidase (MPO) and nitric oxide (NO) in the renal homogenate. Results Data showed significant alteration in serum and urinary creatinine, total protein, albumin, serum urea, blood urea nitrogen (BUN) and uric acid in diabetic animals as compared to the control rats. CoQ10 and/or NAC effectively alleviated the disturbances in renal function. Diabetic rats showed increased MDA, decreased SOD and CAT activities and decreased GSH along with a significant increase in MPO activity and nitrite content. Treatment with the aforementioned antioxidants and their combination ameliorated the kidney damage as indicated by the reduced OS with improved renal function. Conclusion The investigation suggests that the chronic hyperglycaemia-induced OS leads to the development and progression of DN. The combined treatment with CoQ10 and NAC has shown a remarkable nephroprotective effect suggesting that combined antioxidant therapy with CoQ10 and NAC may be useful in the attenuation of DN.

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辅酶Q10单独及联合N-乙酰半胱氨酸对糖尿病肾病的保护作用

目的慢性高血糖引起的氧化应激是糖尿病肾病(DN)及相关肾损伤等多种微血管并发症发生发展的关键因素。抗氧化剂治疗是保护肾脏免受氧化性组织损伤以改善肾脏生理机能的策略之一。因此，本研究旨在评估辅酶Q10 (CoQ10)和n -乙酰半胱氨酸(NAC)单独或联合使用对链脲霉素(STZ)-烟酰胺(NAD)诱导的大鼠糖尿病肾病(DN)的肾保护作用。方法采用STZ (55 mg/kg, i.p)-NAD (110 mg/kg, i.p)诱导Sprague-Dawley大鼠(220 ~ 250 g) T2DM，血糖和糖化血红蛋白升高。通过肾功能检查评估DN。确认糖尿病大鼠DN后，给予辅酶q10 (10 mg/kg, p.o.)和/或NAC (300 mg/kg, p.o.) 8周。通过肾脏匀浆中的丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)、还原性谷胱甘肽(GSH)、髓过氧化物酶(MPO)和一氧化氮(NO)来评估STZ-NAD引起的氧化性组织损伤。结果糖尿病动物血清和尿肌酐、总蛋白、白蛋白、血清尿素、血尿素氮(BUN)、尿酸等指标与对照组相比均有显著变化。辅酶q10和/或NAC可有效缓解肾功能紊乱。糖尿病大鼠MDA升高，SOD和CAT活性降低，GSH降低，MPO活性和亚硝酸盐含量显著升高。用上述抗氧化剂及其联合治疗可以改善肾损伤，这表明OS降低，肾功能改善。结论慢性高血糖诱导的OS可导致DN的发生发展。CoQ10和NAC联合治疗显示出显著的肾保护作用，提示CoQ10和NAC联合抗氧化治疗可能有助于DN的衰减。

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来源期刊

European Pharmaceutical Journal Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

0.60

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0.00%

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