The protective effect of Nigella sativa forms against hepatorenal dysfunction: underlying mechanisms comprise antioxidation, anti-inflammation, and anti-apoptosis

Reham M. Algheshairy^1*Hend F. Alharbi¹Mona S Almujaydil¹Raghad M. Alhomaid¹Hoda Ali²

• ¹Department of Food Science and Human Nutrition, College of Agriculture and Food, Qassim University, KSA. buraydah., Buraydah, Saudi Arabia
• ²Department of Nutrition and Clinical Nutrition, College of Veterinary Medicine, Cairo University, Egypt., cairo, Egypt

The liver and kidney are vital organs related to each other, dealing with detoxifying and excreting xenobiotics, constantly exposed to oxidative stress, causing hepatorenal dysfunction. This study compares two forms of Nigella sativa (NS), NS oil (NSO) and NS seeds (NSS) for the first time, to mitigate hepatorenal injury induced by azathioprine (AZA), comprising potential underlying mechanisms. Group (1): negative control, Group (2): positive control offers 15 mg/kg AZA orally. Groups (3, 4, and 5): received 100 mg/kg silymarin (standard reference), 500 mg/kg NSO, and 250 mg/kg NSS respectively, and were subjected to the same dose of AZA. A one-way analysis of variance was run followed, Mann-Whitney, Post hoc analysis Administration of AZA-induced hepatorenal dysfunction evidenced by dyslipidemia, elevation of serum liver enzymes, creatinine, urea, proinflammatory cytokine, and cytokeratin18. Antioxidant enzymes in liver and kidney tissues were reduced with elevation in caspase-3 and caspase-9. Both forms of NS significantly balanced serum proinflammatory (14.33±2.33, 15.15±1.64 vs 24.87±1.87) pg/ml, Interleukin-4 (16.72±1.14, 15.95±1.03 vs 10.64±1.04) pg/ml, Interleukin-10 (19.89±0.69, 18.38±0.38 vs 15.52±1.02) pg/ml, and downregulated cytokeratin-18 (210.43±21.56, 195.86±19.42 vs 296.54±13.94) pg/ml for NSO and NSS versus positive group respectively. NSS enhanced liver antioxidant activity (P<0.05), normalized liver enzymes (P<0.05, P<0.01) for alanine aminotransferase and aspartate aminotransferase respectively, and significantly lessened dyslipidemia (P<0.05). Liver caspase-3 and caspase-9 improved significantly with NSS while kidney caspase-3 and caspase-9 improved with NSO. NSO increased kidney glutathione peroxidase and catalase (P<0.01) and corrected creatinine and urea (P<0.05). Histopathological observations confirmed the present data. Conclusively, NSO and NSS mitigated hepatorenal dysfunction responses to AZA through antioxidant, anti-inflammatory, and antiapoptosis properties that underlie their protective performance. Interestingly NSO surpassed NSS in restoring renal oxidative damage. Meanwhile, the hepatic protection by NSS was better than NSO, which tends to recommend NSO for patients suffering from kidney dysfunction while using NSS for those who have liver problems.