title: Modulatory role of betulinic acid in N-nitrosodimethylamine-induced hepatorenal toxicity in male Wistar rats.
abstract: N-nitrosodimethylamine (NDMA) is a toxicant found in foods and drinking water. Several synthetic agents used in alleviation of NDMA toxicity have been associated with serious side effects. Therefore, a safe and less toxic agent is desirable. In this study, betulinic acid (BA), a triterpenoid antioxidant, is proposed as a better and alternative agent to modulate NDMA-induced toxicity. Twenty-four Wistar rats were assigned into four groups of six rats each and treated with normal saline (control), BA (25 mg/kg), NDMA (5 mg/kg) and (BA + NDMA). BA was given by oral gavage for 14 consecutive days, while NDMA was administered intraperitoneally on days 7 and 12. Results showed that administration of NDMA significantly ( p < 0.05) elevated the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase and gamma-glutamyl transferase by 51%, 48% and 81%, respectively. Also, NDMA intoxication significantly ( p < 0.05) increased the levels of serum urea and creatinine by 64% and 82%, respectively, and decreased urinary creatinine by 67%. In addition, administration of NDMA significantly ( p < 0.05) increased the levels of hepatic and renal DNA fragmentation by 44% and 61%, respectively, relative to control. The number of micronucleated polychromatic erythrocytes (mnPCEs) in NDMA-treated rats (11.1 ± 2.6 mnPCE/1000PCE) was significantly higher than control (4.3 ± 1.1 mnPCE/1000 PCE). Immunohistochemistry revealed strong expressions of Bcl-2 and nuclear p53 in NDMA-intoxicated rats. Interestingly, pretreatment with BA significantly ( p < 0.05) ameliorated NDMA-induced changes in serum biochemical indices, mnPCEs, DNA fragmentation and expressions of Bcl-2 and p53 proteins. These findings suggest that BA protects against NDMA-induced toxicity via anti-oxidative and anti-apoptotic activities.
authors: 1 Department of Biochemistry, Ladoke Akintola University of Technology, Ogbomoso, Nigeria.
authors: G E
authors: GE
authors: Adeleke
authors: 2 Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
authors: O A
authors: OA
authors: Adaramoye
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017208:Rats, Wistar; D014315:Triterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014508:Urea / Q000097:blood; D000094062:Betulinic Acid
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D053978:Pentacyclic Triterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; D014508:Urea; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D004128:Dimethylnitrosamine; D000094062:Betulinic Acid
keywords: DNA fragmentation; N-nitrosodimethylamine; betulinic acid; micronucleated polychromatic erythrocytes