Abstract
Immunosuppressants are used clinically to lower rejection rates in transplant patients. Unfortunately, the adverse side effects of these immunosuppressants can be severe, which is one of the rationales that life expectancy of individuals after transplant still significantly falls short of that of the general population. The current experimental setup was designed to analyze the tacrolimus-induced hepatic iron overload in Wistar rats. Four experimental groups were orally given 1 ml of aqueous suspension of tacrolimus (12 mg/kg) through oral gavage, and rats were sacrificed after 6, 12, 24, and 48 h of tacrolimus dose. Hepatic hepcidin expression was found to be significantly augmented along with the upregulation of Tf and TfR1, Ferritin-L, Ferritin-H, TNF-α, and HO-1 gene expression at 6 and 12 h, and downregulation of Fpn-1, Hjv, and Heph at 6 h was detected. Significant downregulation of IL-6, IFN-α, IFN-β, and IFN-γ at all study time points was also observed. Serum iron level was decreased while serum hepcidin level was found to be significantly increased. Iron staining showed blue-stained hemosiderin granules within the hepatocytes, sinusoidal spaces, and portal areas at 12 and 24 h time points and remarkable fall of iron contents in the splenic red pulp. These results suggest that the use of tacrolimus leads to the onset of an intrahepatic acute-phase response-like reaction and causes iron overload in hepatic cells by altering the expression of key proteins involved in iron metabolism.
Highlights
Transplantation is a lifesaving intervention for the patients suffering from organ failure at end stages and transplantation medication plot is one of the foremost complex and challenging area of a modern medical system [1]
The expression of different iron regulatory genes was analyzed at different time points to assess the disturbances in iron metabolism
A significant increase was noted in Heme oxygenase (HO)-1 expression at 6 h (2:89 ± 0:25-fold) which reached a peak at 12 h (3:06 ± 0:30-fold), and after 12 h, HO-1 expression starts to decline towards baseline level, while a significant downregulation of HO-1 expression was observed at 48 h time point (1:047 ± 0:23-fold) as compared to 12 h time point (3:06 ± 0:30-fold) upregulation when analyzed by Tukey’s post hoc test (Figure 1(b))
Summary
Transplantation is a lifesaving intervention for the patients suffering from organ failure at end stages and transplantation medication plot is one of the foremost complex and challenging area of a modern medical system [1]. Patients after organ transplantation are forced to take lifelong immunosuppressive drugs to suppress the immunity and stabilize the transplant in the body of the patient [2]. All immunosuppressant used in transplant can be considered a high-risk medication. Tacrolimus is a pivotal immunosuppressive drug used clinically to lower the rate of immunological rejection after solid organ transplantation [3]. It is well known that its immunosuppressive possessions are dependent on calcineurin inhibition [4, 5]. Due to the inhibition of calcineurin, tacrolimus modifies several biochemical processes, which can lead to undesirable side effects [6, 7]. Anemia is common after transplantation, and immunosuppressants have long been involved in the pathogenesis of anemia after transplantation [8]
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