Decreased Expression of Alpha Smooth Muscle Actin and Desmin Contributes to the Protection of Vitamin D3 against Diclofenac Induced Nephrotoxicity in Rats
Abstract
Background: Diclofenac is widely prescribed for its analgesic and anti-inflammatory actions but it also has some harmful effects on the kidney. The current study was conducted to elucidate the possible mechanism of action of diclofenac sodium on kidney, and if it is affected by the addition of vitamin D.
Methods: Rats were divided into 4 equal groups. G1 was the control group that received no treatment; G2 was treated with intramuscular injection of vitamin D (1,000 IU/kg, 3days/week); G3 was treated with intramuscular injection of diclofenac sodium (3.6 mg/kg, 3 days/week) and G4 treated simultaneously with both diclofenac (3.6 mg/kg, 3 days/week) and vitamin D (1,000 IU/kg, 3days/week) intramuscularly for four weeks. Kidneys sections were stained with H&E, Masson’s trichrome and immunohistochemical staining against α –SMA and desmin followed by the morphometric and statistical analysis.
Results: Kidney sections from diclofenac sodium treated group showed degeneration and necrosis, small or atrophic glomeruli with dilated Bowman’s space and some of the renal tubular lining cells appeared vacuolated with small pyknotic nuclei. Renal fibrosis was confirmed by significant increase in collagen fibers, α –SMA and podocytes injury by significant increase of desmin. However, in diclofenac- vitamin D treated group significantly the expression of α –SMA and desmin were decreased.
Conclusion: The current data suggested that vitamin D might play a protectant role against diclofenac induced kidney injury in rats through the preservation of the histological architecture of renal corpuscles, renal cortical tubules and down regulation of collagen, α – SMA and desmin.
Keywords: α-SMA; Desmin; Diclofenac Sodium; Vitamin D
Full Text:
PDFReferences
El-Maddawy Z, El-Ashmawy I. Hepato-Renal and Hematological Effects of Diclofenac Sodium in Rats. Global Journal of Pharmacology, (2013); 7 (2): 123-132.
Pandey PK, Ajima MNO, Kumar K, Poojary, N, Kumar S. Evaluation of DNA Damage and Physiological Responses in Nile Tilapia, Oreochromis niloticus (Linnaeus, 1758) Exposed to Sub-Lethal Diclofenac (DCF). Aquatic Toxicology, (2017); 186: 205-214.
Altman R, Bosch B, Brune K, Patrignani P, Young C. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs, (2015); 75(8) pp. 859-877.
Ng LE, Vincent AS, Halliwell B, Wong KP. Action of diclofenac on kidney mitochondria and cells, Biochemical and Biophysical Research Communications, (2006); 348(2): 494–500.
Chouhan S, Sharma S. Renal damage: a possible role of diclofenac induced injury associated with altered acid phosphatase and collagen content in Balb/c mice. Proceedings of the National Conference on ‘Advances in Basic & Applied Sciences’. Asian Journal of Advanced Basic Sciences, (2014); 2(3): 116-124.
Elbassuoni EA, Ragy MM, Ahmed SM. Evidence of the protective effect of l-arginine and vitamin D against monosodium glutamate-induced liver and kidney dysfunction in rats. Biomedicine and Pharmacotherapy, (2018); 108: 799–808.
Zhang Y, Deb DK, Kong J, Ning G, Wang Y, et al. Long-term therapeutic effect of vitamin D analog doxercalciferol on diabetic nephropathy: strong synergism with AT1 receptor an¬tagonist. American Journal Physiology -Renal Physiology, (2009); 297(3): F791-F801.
Zhang Z, Yu X, Fang X, Liang A, Yu Z, et al. Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis. Scientific Reports, (2015); 5: 17638.
Abu-Mouch S, Fireman Z, Jarchovsky J, Zeina AR, Assy N. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naive patients. World Journal of Gastroenterology, (2011); 17(47) 5184–5190.
BaSalamah MA, Abdelghany AH, El-Boshy M, Ahmad J, Idris S and Refaat B: Vitamin D alleviates lead-induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats. Scientific Reports, (2018); 8 (4853): 1-13.
Mustafa H, Alkan I, Deniz Ö, Altunkaynak Z, Annaç E et al. A Study on the Toxic Effect of Different Doses of Diclofenac Sodium on the Development of the Kidney in the Postnatal Period. International Journal of Morphology, (2019); 37 (3): 877-884.
Bancroft JD, Layton C. The Hematoxylin and eosin, connective and mesenchymal tissues with their stains. In: Suvarna SK, Layton C and Bancroft JD, editors. Bancroft’s theory and practice of histological techniques. 7th edition. Churchill Livingstone: Philadelphia. 2013; 173- 212.
Youssef S, Mohamed S B. Impact of Finasteride Administration on Neuroactive Steroid Levels to Induce Persistent Sexual Side Effects and Anxious/Depressive Disorders and the Possible Protective Effect of Vitamin E. International Research Journal of Applied and Basic Sciences, (2017); 11 (2): 200-220.
Youssef S. Light and Electron Microscopic Study of the Effect of Orlistat on the Liver of Adult Male Albino Rats and the Possible Protective Role of β-Carotene. Forensic Medicine and Anatomy Research, (2018); 6(2): 20-36.
AbdEl-Moniem M, Mustafa HN, Megahed HA, Agaibyi MH, Hegazy G, et al. The ameliorative potential of Hyphaene thebaica on streptozotocin induced diabetic nephropathy. Folia Morphologica, (2015); 74(4):447-57.
Hassan SA, Sabry DA, Hussein MA. Protective Effect of Cranberry Extracts against Oxidative Stress and DNA Damage Induced by Diclofenac Sodium in Kidney of Male Albino Rat. Chinese Medicine, (2017); 8: 113-131.
Siva T, Sivakumar G , Sankaran P K, Francis M, Gayathri T, et al. Hepatorenal profile of diclofenac sodium in wistar rats. Drug Invention Today, (2019); 12 (9): 1908-19012.
Fattori V, Borghi SM, Guazelli CFS, et al. Vinpocetine reduces diclofenac-induced acute kidney injury through inhibition of oxidative stress, apoptosis, cytokine production, and NF-κB activation in mice. Pharmacological Research, (2017); 120:10-22.
Galesic K, Ljubanovic D, Bulimbasic S, Racic I. Minimal change disease and acute tubular necrosis caused by diclofenac. Nephrology (Carlton), (2008); 13: 187–88.
Aycan IO, Elpek O, Akkaya B, Kıraç E, Tuzcu H, et al. Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment. Food and Chemical Toxicology, (2018); 118: 795–804.
Youssef S, Salah M. Renal Cortical Structural Alterations in Atorvastatin treated Rats and the Possible Protective Mechanisms of L-Carnitine. Indian Journal of Pharmaceutical Sciences, (2019); 81(5):834-843.
Emanuel R. Essential Pathology, third ed. Lippincot Williams & Wilkins, 2001; pp.1.
Kumar V, Abbas AK, Aster JC. Robbins & Cotran. Pathologic Basis of Disease, ninth ed. Elsevier Saunders, Philadelphia (US), 2015; pp. 42.
Pawlina W. Histology a text and atlas with correlated cell and molecular biology, 7th ed. Wolters Kluwer, Philadelphia, Baltimore, New York, London. 2016; pp 698 -699, pp 91- 94 and P.720.
Khoshvakhti H, Yurt KK, Altunkaynak BZ, Turkmen AP, Elibol E, et al. Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study. Renal Failure, (2015); 37(8): 1379–1383.
DePhillipo NN, Aman ZS, Kennedy MI, Begley JP, Moatshe G, et al. Efficacy of Vitamin C Supplementation on Collagen Synthesis and Oxidative Stress After Musculoskeletal Injuries: A Systematic Review. Orthopedic Journal of Sports Medicine, (2018); 6(10) 1-9.
Baher W, Abo Zeid, A, Abd Al-Khalek H. The Possible Protective and Therapeutic Effects of Mesenchymal Stem Cells Compared to Vitamin C in Gentamicin Induced Acute Kidney Injury in Adult Rats. A Histological Study. Egyptian Journal of Histology, (2019); 42(4):738-796.
Abdel-Hamid G. Effect of Red Grape Juice on Renal Glomeruli in Hypercholestremic Rats. Life Science Journal, (2014); 11(6):234-245.
Xiao Q, Guan Y, Li C, Liu L, Zhao D, et al. Decreased expression of transforming growth factor-β1 and α-smooth muscle actin contributes to the protection of lotensin against chronic renal failure in rats. Renal Failure, (2018); 40(1): 583–589.
Rastaldi MP. Epithelial-mesenchymal transition and its implications for the development of renal tubulointerstitial fibrosis. Journal of Nephrology, (2006); 19(4):407–412.
Yousry MM, Farag EA, Omar Al. Histological Study on the Potential Effect of Sildenafil on the Kidney and Testosterone Level in Experimentally Induced Diabetes in Male Rats. Journal of Cytology and Histololgy, (2016); 7 (4): 1-8.
Gao F, He X, Liang S, Liu S, Liu H, He Q, Chen L, Jiang H, Zhang Y. Quercetin ameliorates podocyte injury via inhibition of oxidative stress and the TGF-b1/Smad pathway in DN rats. RSC Advances, (2018); 8 (62): 35413–35421.
Shalaby A, El Shaer D. Lycopene protects against renal cortical damage induced by nandrolone decanoate in adult male rats. Annals of Anatomy, (2019); 224: 142–152.
Kubesch A, Quenstedt L, Saleh M, Ruschenbaum S, Schwarzkopf K, Martinez Y, et al. Vitamin D deficiency is associated with hepatic decompensation and inflammation in patients with liver cirrhosis: a prospective cohort study. PLoS ONE, (2018); 13(11): e0207162.
Almaimani RA, Almasmoum H, Ghaith MM, et al. Enhanced remedial effects for vitamin D3 and calcium co-supplementation against pre-existing lead nephrotoxicity in mice: the roles of renal calcium homeostatic molecules, Biochimica et Biophysica Acta – Molecular Basis of Disease, (2019); 1865)2): 512–524.
Elbassuoni E, Ragy M, Ahmed S. Evidence of the protective effect of L-arginine and vitamin D against monosodium glutamate-induced liver and kidney dysfunction in rats. Biomedicine & Pharmacotherapy, (2018); 108: 799–808.
Ramirez A M, Wongtrakool C, Welch T, Steinmeyer A, Zügel U, Roman J. Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells The Journal of Steroid Biochemistry and Molecular Biology, (2010); 118(3):142–150.
El-Gerbed MS. Protective effect of lycopene on deltamethrin-induced histo-logical and ultrastructural changes in kidney tissue of rats. Toxicology and Industrial Health, (2014); 30(2): 160–173.
DOI: http://dx.doi.org/10.62940/als.v8i1.966
Refbacks
- There are currently no refbacks.