Research Articles

2019  |  Vol: 5(1)  |  Issue: 1(January-February)  |  https://doi.org/10.31024/ajpp.2019.5.1.28

Forskolin, ameliorates mitochondrial dysfunction in Streptozotocin induced diabetic nephropathy in rats

Surbhi Rana¹, Lakhwinder Singh²*, Sidharth Mehan³

¹Research Scholar, I. K. Gujral Punjab Technical University, Jalandhar, Punjab, India  

²Head Department of Applied Science CGC College of Engineering, Landran, Punjab, India

³Associate Professor, Department of Pharamcology, ISF College of Pharmacy, Moga, Punjab, India

*Address for Corresponding Author

Lakhwinder Singh

Head Department of Applied Science CGC College of Engineering,

Landran, Punjab, India-140307

Abstract

Objective: Diabetes downregulates the expression of nitric oxide and elevate the reactive oxygen species resulting in oxidative stress leads to mitochondrial dysfunction. In the present study we have examined the role of Forskolin in reduced nitric oxide and mitochondrial dysfunction, which may be responsible for the development of diabetic nephropathy. Materials and methods: Diabetes mellitus in rats was induced by feeding high fat diet (HFD) for 2 weeks followed by single low dose of Streptozotocin (STZ) 35mg/kg, i.p. further followed by HFD for next ten weeks. STZ administered rats exhibited apparent renal functional changes as compared to normal rats. These renal functional abnormalities were complimented with increased uric acid, liver functions and mitochondrial complexes dysfunction as assessed in terms of mitochondrial Adenosine Triphosphate (ATP) levels in Liver, Kidney and Pancreas, Alkaline Phosphatase (ALP), Succinate Dehydrogenase (SDH), Nicotinamide Adenine Dinucleotide Phosphate (NADPH), Lactate Dehydrogenase (LDH). Results: Two weeks treatment with Forskolin presented a marked renoprotection by significantly preventing renal abnormalities supported by biomarkers of mitochondrial and liver dysfunctions tests. Conclusion: Hyperglycaemia produces mitochondrial dysfunction with dysregulation between oxidative stress and nitric oxide. Diminished nitric oxide level, elevated uric acid, liver and mitochondrial dysfunction could play critical role in STZ induced mitochondrial dysfunction in diabetic nephropathy. This study provides preliminary evidences that Forskolin markedly prevented mitochondrial dysfunction and progression of nephropathy.  

Keywords: Mitochondrial dysfunction, mesangial expansion, oxidative stress, Forskolin