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Ameliorative role of inducible nitric oxide synthase inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats.

Authors :
Kumar Sharma, Ashwani
Kaur, Anmoldeep
Kaur, Tajpreet
Kaur, Sarabjit
Pathak, Devendra
Singh, Amrit Pal
Source :
Drug & Chemical Toxicology; Sep2022, Vol. 45 Issue 5, p2255-2261, 7p
Publication Year :
2022

Abstract

Arsenic exposure causes immense health distress by increasing risk of cardiovascular abnormalities, diabetes mellitus, neurotoxicity, and nephrotoxicity. The present study explored the role of inducible nitric oxide synthase (iNOS) inhibitors against sodium arsenite-induced renal and hepatic dysfunction in rats. Female Sprague Dawley rats were subjected to arsenic toxicity by administering sodium arsenite (5 mg/kg/day, oral) for 4 weeks. The iNOS inhibitors, S-methylisothiourea (10 mg/kg, i.p.) and aminoguanidine (100 mg/kg, i.p.) were given one hour before sodium arsenite administration in rats for 4 weeks. Sodium arsenite led rise in serum creatinine, urea, uric acid, electrolytes (potassium, fractional excretion of sodium), microproteinuria, and decreased creatinine clearance (p < 0.001) indicated renal dysfunction in rats. Arsenic-intoxication resulted in significant oxidative stress in rat kidneys, which was measured in terms of increase in lipid peroxides, superoxide anion generation and decrease in reduced glutathione (p < 0.001) levels. A threefold increase in renal hydroxyproline level in arsenic intoxicated rats indicated fibrosis. Hematoxylin–eosin staining indicated tubular damage, whereas picrosirius red staining highlighted collagen deposition in rat kidneys. S-methylisothiourea and aminoguanidine improved renal function and attenuated arsenic led renal oxidative stress, fibrosis, and decreased the kidney injury score. Additionally, arsenite-intoxication resulted in significant rise in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, and bilirubin (p < 0.001) along with multi-fold increase in oxidative stress, fibrosis and liver injury score in rats, which was significantly (p < 0.001) attenuated by concurrent administration of iNOS inhibitors). Hence, it is concluded that iNOS inhibitors attenuate sodium arsenite-induced renal and hepatic dysfunction in rats. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
01480545
Volume :
45
Issue :
5
Database :
Complementary Index
Journal :
Drug & Chemical Toxicology
Publication Type :
Academic Journal
Accession number :
159132627
Full Text :
https://doi.org/10.1080/01480545.2021.1926109