Immunosuppressant drug tacrolimus induced mitochondrial nephrotoxicity, modified PCNA and Bcl-2 expression attenuated by Ocimum basilicum L. in CD1 mice

• Published in: Toxicology reports 2018-01, Vol.5, p.687-694
• Main Authors: Oyouni, Atif Abdulwahab A., Saggu, Shalini, Tousson, Ehab, Rehman, Hasibur
• Format: Article
• Language: English
• Subjects: Bcl-2; Nephrotoxicity; Ocimum basilicum; PCNA; Tacrolimus
• ISSN: 2214-7500; 2214-7500
• DOI: 10.1016/j.toxrep.2018.06.003

[Display omitted] •Tacrolimus (TAC), an immunosuppressant drug has been demonstrated to augment free radical production.•It increased serum creatinine, BUN and oxidative deterioration of cellular tissues in CD-1 mice.•TAC-induced nephrotoxicity altered the mitochondrial antioxidant defense, expression of PCNA, Bcl2.•TAC-induced changes are ameliorated by pretreatment of Ocimum basilicum L (OB).•OB can be considered as a potential source of antioxidants, phenols, alkaloids with potent nephroprotective activity. Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC50) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P