Possible Protective Effect of Diacerein on Doxorubicin-Induced Nephrotoxicity in Rats

Abstract

Nephrotoxicity is one of the limiting factors for using doxorubicin (DOX). Interleukin 1 has major role in DOX-induced nephrotoxicity, so we investigated the effect of interleukin 1 receptor antagonist diacerein (DIA) on DOX-induced nephrotoxicity. DIA (25 and 50 mg/kg/day) was administered orally to rats for 15 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg/kg) at the 11th day. We measured levels of serum urea, creatinine, renal reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx), catalase, and superoxide dismutase (SOD). In addition, caspase-3, tumor necrosis factor alpha (TNFα), nuclear factor kappa B (NFκB) expressions, and renal histopathology were assessed. Our results showed that DOX-induced nephrotoxicity was ameliorated or reduced by both doses of DIA, but diacerein high dose (DHD) showed more improvement than diacerein low dose (DLD). This protective effect was manifested by significant improvement in all measured parameters compared to DOX treated group by using DHD. DLD showed significant improvement of creatinine, MDA, NOx, GSH, histopathology, and immunohistochemical parameters compared to DOX treated group.

The role of interleukin‐1b and its antagonist (diacerein) in estradiol benzoate‐induced endometrial hyperplasia and atypia in female rats

“…Co‐administration of DIA to EB‐treated rats showed significant increase in SOD activity compared with EB‐treated rats alone. That is consistent with Refaie et al .…”

“… Group I was received vehicle of DIA (1% carboxymethylcellulose) and intramuscular (im) olive oil three times per week for 4 weeks . Group II was treated with DIA (50 mg/kg/day orally) and im olive oil 3 times per week for 4 weeks . Group III was treated with vehicle of DIA (1% carboxymethylcellulose) and im injection of EB (60 μg/100 g) three times per week for 4 weeks . Group IV was treated with DIA (50 mg/kg/day orally) + im injection of EB (60 μg/100 g) three times per week for 4 weeks . …”

“…Diacerein (DIA) is an anti‐inflammatory, analgesic, and antipyretic drug, developed for treatment of osteoarthritis . DIA inhibits the production of IL‐1b by human monocytes.…”

Organic anion transporters 1 (OAT1) and OAT3 meditated the protective effect of rhein on methotrexate-induced nephrotoxicity

“…It was reported that diacerein, the prodrug of rhein, protected against doxorubicin-induced nephrotoxicity in rats most probably due to its antioxidant and anti-inammatory activities. 41 Similarly, Zhao et al demented that protective effect of rhein against acetaminophen-induced kidney injuries might result from the amelioration of oxidative stress. 42 Interestingly, Meng et al also demonstrated that rhein signicantly alleviated the symptoms of nephropathy through decreasing the production of proinammatory cytokines, including interleukin 1b, prostaglandin E2, and TNFa.…”

Ameliorative effect of Cubeba Officinalis dried fruits against Tacrolimus induced nephrotoxicity in Wistar albino rats

“…Immunosuppressive agents suppress the immune system in order to avoid graft rejections after organ transplantation.These agents, especially tacrolimus and cyclosporine, are associated with the high risk of toxicities, including renal toxicity, neurotoxicity, etc. (Refaie et al, 2016). After the induction of the nephrotoxicity using tacrolimus, there was a signi icant reduction in the blood urea nitrogen (BUN) serum creatinine and a raise in serum uric acid (Soumya et al, 2011).…”