اثر عصاره متانولی برگ Momordica charantia بر نفروپاتی ناشی از آلوکسان از طریق تعدیل مسیرهای سیگنالینگ BCL2 / NF-kB در موش صحرایی

Subject Areas : Journal of Medicinal Herbs, "J. Med Herb" (Formerly known as Journal of Herbal Drugs or J. Herb Drug)

ساندی افوبه ¹ , آدمولا اویابمی ² , تمیدایو اوبوموال ³ , ادورابنرو آدداپو ⁴ , آبیدون آدوله ⁵ , مومو یاکوبو ⁶ , آلوفمی انتیبجو ⁷ , آدلو آدداپو ⁸

1 - گروه داروسازی و سم شناسی دامپزشکی ، دانشکده دامپزشکی ، دانشگاه ابادان ، نیجریه.
2 - گروه فیزیولوژی و بیوشیمی دامپزشکی ، دانشکده دامپزشکی ، دانشگاه ابادان ، نیجریه.
3 - گروه دامپزشکی ، دانشکده دامپزشکی ، دانشگاه ابادان ، نیجریه.
4 - گروه دارویی و درمانی ، کالج پزشکی ، دانشگاه ابادان ، نیجریه
5 - گروه گیاه شناسی ، دانشکده علوم ، دانشگاه ابادان ، نیجریه
6 - گروه علوم محیطی و بین رشته ای ، کالج علوم ، مهندسی و فناوری ، دانشگاه جنوب تگزاس ، هوستون ، TX ، ایالات متحده آمریکا
7 - مرکز تحقیقات استرس اکسیداتیو، فیتو پزشکی و فیتوشیمی ، دانشکده علوم بهداشت و سلامتی ، دانشگاه فناوری شبه جزیره کیپ ، بلویل ، 7535 ،
8 - گروه داروسازی و سم شناسی دامپزشکی ، دانشکده دامپزشکی ، دانشگاه ابادان ، نیجریه.

Received: 2020-06-11 Accepted : 2020-09-29 Published : 2019-12-22

Keywords: Antioxidant, Diabetes mellitus, Antidiabetic, Momordica charantia, kidney injury,

Abstract :

Background & Aim: Nephropathy is one of the major complications of diabetes with oxidative stress as one of the possible mechanisms mediating the event. Natural products with antioxidant property may be a promising therapeutic approach to ameliorate renal damage from diabetic nephropathy hence the renoprotective activity of methanolic leaf extract of Momordica charantia (MEMC) was assessed. Experimental:  The effects of MEMC on alloxan-induced nephrotoxicity were examined where toxicity was induced by intraperitoneal administration of alloxan to 50 rats divided into five groups of 10 rats each. MEMC was administered to two groups at the doses of 200 and 400 mg/kg for 28 days; glibenclamide administered to another group of diabetic rats. While another group was left untreated, a group of normal rats received only distilled water. Nephroprotective effect of the extract was studied by assessing its effect on oxidative stress markers, antioxidant defence system, immunohistochemistry, histological and serum urea and creatinine analysis. Results:  Alloxan administration altered renal biomarkers (increased serum urea and creatinine levels), increased renal H2O2 malondialdehyde levels, and decreased reduced glutathione, glutathione peroxidase, catalase, and superoxide dismutase. Histological studies showed glomerular degeneration and hypercellularity. However, administration of glibenclamide (4 mg/kg) and MEMC ameliorated the alloxan-induced nephrotoxicity. Immunohistochemical studies revealed lower expressions of BCL2 but greater expressions of NF-κB in the kidney of the toxicant non-treated rats compared with the control, glibenclamide treated and MEMC treated rats. Recommended applications/industries: MEMC showed renoprotective activity in alloxan-induced nephropathy mediated through its antioxidant and anti-inflammatory activities. This extract could be used in the treatment of acute kidney failure.

References:

Barutta F., Bruno G., Grimaldi S. and Gruden G. 2015. Inflammation in diabetic nephropathy: moving toward clinical biomarkers and targets for treatment. Endocrine, 48: 730-742.

Betty R.K. and Jonathan A.C. 2003. Essential Medical Statistics. USA: Blackwell. pp. 409.

Drury R.A., Wallington E.A and Cancerson R (1976). Carlton’s Histopathological Techniques. Oxford: Oxford University press.pp. 279-280.

Farmer E.E. and Davoine C. 2007. Reactive electrophile species. Current Opinion Plant Biology, 10: 380-386.

Ha H., Park J.H. and Lee H.B 2008. Role of reactive oxygen species in the pathogenesis of diabetic nephropathy. Diabetes Research and Clinical Practice, 82: 42-45.

Habig W.H., Pabst M.J. and Jakoby W.B. 1974. Glutathione-S-transferases: The first enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 25: 130-139.

Hakim F.A. and Pflueger A. 2010. Role of oxidative stress in diabetic kidney disease. International Medical Journal and Experimental Clinical Research, 16: 37-48.

Han H., Aili C., Wang L., Guob H., Zanga Y., Zezheng L. 2017. Decoction ameliorates streptozotocin-induced rat diabetic nephropathy through antioxidant and regulation of the TGF-b/MAPK/PPAR-γ signaling. Cell Physiology and Biochemistry, 42: 1934-1944.

Harinantenaina L., Tanaka M. and Takaoka S. 2006. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chemical Pharmacological Bulletin, 54: 1017-1021.

Hooper D., Spitsin S., Kean R., Champion J., Dickson G., and Chaudhry I. 1998. Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis. Proceeding of National Academy of Science, 95: 675-680.

Jain E.C. 2012. Histopathological changes in diabetic kidney disease. Clinical Queries: Nephrology,102: 127–133.

Jollow D.J., Mitchell J.R., Zampaglione N. and Gillette J.R. 1974. Bromobenzene-induced liver necrosis: Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology, 11: 151-169.

Kawahito S., Kitahata H. and Oshita S. 2009. Problems associated with glucose toxicity: Role of hyperglycemia-induced oxidative stress. World Journal of Gastroenterology, 15: 4137.

Kim J.Y., Lee S.H., Song E.H., Park Y.M., Lim J.Y. and Kim D.Y. 2009. A critical role of STAT1 In streptozotocin-induced diabetic liver injury in mice: controlled by ATF3. Cell Signalling, 21: 1758–1767.

Krawinkel M.B. and Keding G.B. 2006. Bitter gourd (Momordica Charantia): A dietary approach to hyperglycemia. Nutritional Review, 64: 331-337.

Misra H.P. and Friedovich I. 1972. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for super oxide dismutase. Journal of Biological Chemistry, 25: 3170-3175.

N.I.H. National Institute of Health, Guide for the care and use of Laboratory Animals U.S. Department of Health Education and welfare, 1985.

Oyagbemi A.A., Omobowale T.O., Akinrinde A.S., Saba A.B., Ogunpolu B.S. and Daramola O. 2015. Lack of reversal of oxidative damage in renal tissues of lead acetate-treated rats. Environmental Toxicology, 30: 1235–1243.

Park K.S., Kim J.H., Kim M.S., Kim J.M., Kim S.K., Choi J.Y. 2001. Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes, 50: 837- 841.

Reuter S., Gupta S.C., Chaturvedi M.M. and Aggarwal B.B. 2010. Oxidative stress, inflammation and cancer: how are they linked? Free Radical Biology and Medicine, 49: 1603–1616.

Rotruck J.T, Pope A.L., Ganther H.E., Swanson A.B., Hafeman D.G., Hoekstra W.G. 1973. Selenium: biochemical role as a component of glutathione peroxidise. Science, 179: 588–590.

Sedlak J. and Lindsay R.H. 1968. Estimation of total protein-bound and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 25: 1192-1105.

Senthilkumar S., Yogeeta S.K., Subashini R. and Devaki T. 2006. Attenuation of cyclophosphamide induced toxicity by squalene in experimental rats. Chemical and Biological Interaction, 160: 252–260.

Shertzer H.G., Sainsbury M. and Berger M.L. 1990. Importance of protein thiols during N-methyl-N''''-nitro-N-nitrosoguanidine toxicity in primary rat hepatocytes: Toxicological and Applied Pharmacology, 105: 19–25.

Singh D., Chander V and Chopra K. 2004. Protective effect of naringin, a bioflavonoid on glycerol-induced acute renal failure in rat kidney. Toxicology, 201: 143–151.

Subramanian S., Narayanasamy N., Venkatesan G. and Kalichamy C. 2012. In vivo antioxidant potential of Momordica charantia against cyclophosphamide-induced hepatic damage in rats. International Journal of Biological Chemistry, 6: 89-96.

Tak P.P. and Firestein G.S. 2001. NF-kappa B: A key role in inflammatory diseases. Journal of Clinical Investigation, 107: 7–11.

Tamay-Cach F., Quintana-Pe´rez J.C., Trujillo-Ferrara J.G., Cuevas-Herna´ndez R.L., Del Valle-Mondragon L., Garcıa-Trejo E.M. 2016. A review of the impact of oxidative stress and some antioxidant therapies on renal damage. Renal Failure, 38: 171–175.

Thenmozhi A.J. and Subramanian P. 2011. Antioxidant potential of Momordica charantia in ammonium chloride-induced hyperammonemic rats. Evidence-based Complementary and Alternative Medicine, 1-7.

Varshney R. and Kale R.K. 1990. Effect of Calmodulin antagonists on radiation induced lipid peroxidation in microsomes. International Journal of Radiation Biology, 58: 733-743.

Veal E.A., Day A.M., Morgan B.A., Morgan D. 2007. Hydrogen peroxide sensing and   signalling: Molecules and Cell, 26: 1–14.

Vinothini G., Manikandan P., Anandan R. and Nagini S. 2009. Chemoprevention of rat mammary carcinogenesis by Azadirachta indica leaf fractions: modulation of hormone status, xenobiotic-metabolizing enzymes, oxidative stress, cell proliferation and apoptosis. Food and Chemical Toxicology, 47: 1852–1863.

Wolff S.F. 1994. Ferrous ion oxidation in the presence of ferric ion indicator xylenol orange for measurement of hydrogen peroxides. Methods in Enzymology, 233:182-189.

Xu W.L., Li Y.Z., Zhang Q.S. and Zhu H.S. 2004. A selective, convenient, and efficient conversion of sulfides to sulfoxides. Synthesis, 2: 227-232.

Zygner W., Gojska-Zygner O., Baska P. and Dlugosz E. 2014. Increased concentration of serum TNF alpha and its correlations with arterial blood pressure and indices of renal damage in dogs infected with Babesia canis. Parasitological Research, 113:1499-1503.