Abstract
Tacrolimus is a powerful immunosuppressive agent with hepatotoxic and nephrotoxic effects. It has a protective role against many toxicants. This study was conducted to evaluate the possible protective role of spirulina against tacrolimus induced hepatotoxicity and nephrotoxicity. Forty adult male albino rats divided into 4 groups. Group I, control group, Group II, spirulina group (received spirulina 500 mg/Kg body weight (bw)/day orally), Group III, tacrolimus group (received tacrolimus 12 mg/kg bw/day orally); and Group VI, prophylactic group (orally administered spirulina for 3 days before and 28 days concurrently with tacrolimus in the same previous doses). Tacrolimus induced adverse effects on both liver and kidney functions and structure that was manifested by elevated hepatic transaminases, total and direct bilirubin, albumin, blood urea nitrogen, serum creatinine and creatinine clearance. There was a significant decrease in serum total antioxidant capacity (TAC) and hepatic and renal total thiol molecules (TTM), with a significant increase in serum malondialdehyde in tacrolimus group. Histopathologically, tacrolimus induced swelling and granulation of hepatocytes, congestion of blood sinusoids and degeneration of bile ductiles, glomerular hypertrophy and segmentation, swelling, degeneration and hyalinosis of renal tubules. Spirulina pre- and co-treatment significantly improved these deleterious effects. This was accompanied by partial restoration of the expression of PCNA near to the normal level observed in control rats. Moreover, spirulina treatment did not alter the trough blood tacrolimus levels or tacrolimus-induced immunosuppression. Further studies are warranted to evaluate whether transplant patients on tacrolimus treatment may benefit from the protective effects of spirulina. Key words: Antioxidant, malondialdehyde (MDA), total antioxidant capacity (TAC), tacrolimus, total thiol molecules (TTM), proliferating cell nuclear antigen (PCNA), spirulina.
Highlights
Tacrolimus is an immunosuppressant macrolide produced by Streptomyces tsukubaenesis
Rats treated by tacrolimus showed a significant increase in serum ALT, AST, Alkaline phosphatase (ALP), total and direct bilirubin, as well as Blood urea nitrogen (BUN), serum creatinine and a significant decrease in albumin and creatinine clearance compared to control rats
Tacrolimus is an immunosuppressive drug that binds to protein and inhibits the phosphatase activity of calcineurin in T lymphocytes to reduce the activity of the
Summary
Tacrolimus is an immunosuppressant macrolide produced by Streptomyces tsukubaenesis. Protocols that do not include calcineurin inhibitors often is associated with limited graft survival that makes tacrolimus considered as the backbone of most immunosuppressive regimens (Jantz et al, 2013). Patients receiving tacrolimus chronically are at high risk to develop cholestasis and renal damage (Yadav et al, 2013; Banhara et al, 2015). Histopathologic examination revealed that tacrolimus induces renal necrosis and apoptosis. It increases reactive oxygen species production and decreases antioxidant status (Piao et al, 2014). A big need arises to alleviate tacrolimus induced oxidative stress or to reduce its dose to a safer level. Reducing tacrolimus dose can impair its therapeutic efficacy
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