Unravelling the Protective Effects of Emodin Against Cyclophosphamide Induced Gonadotoxicity in Male Wistar Rats

Abstract

Background Over the past few decades, cyclophosphamide (CP) has been extensively used as a broad-spectrum alkylating agent for the treatment of various cancers and solid tumors. However, the therapeutic actions on CP are not limited to only cancer cells, as it simultaneously exerts significant toxicities on healthy cells through the instigation of oxidative stress and oxidative damages. CP induced testicular toxicity is associated with impaired spermatogenesis, reduced sperm functionality, reproductive hormone and testicular weight. This study was aimed at unravelling the protective effects of emodin (EMD) on testicular toxicity following CP treatment. Methods Twenty-four male Wistar rats were allotted into 4 groups as normal control group (NCG), CP control group (CPCG), EMD25+CP (25 mg/kg in 5% tween 80) and EMD50+CP groups (50 mg/kg in 5% tween 80). EMD was orally administered for 35 consecutive days, while four doses of CP (100 mg/kg/week) were administered intraperitoneally from the second to fifth week of treatment. Thereafter, the animals were sacrificed and histopathological examination of the testes as well as serum/testicular biochemical assays were conducted. Results The results revealed that CP significantly impeded sperm function parameters including sperm count, viability and motility as well as decreased reproductive hormones (testosterone, LH and FSH) levels. In addition, CP enhanced testicular oxidative stress and proinflammatory markers (MDA, IL-6 and TNF-α), while simultaneously decreasing testicular antioxidant enzymes (GSH, GPx, SOD and CAT). Evidence of marked histopathological alterations was also observed in the H&E stained testicular tissues of CP treated rats. EMD significantly prevented these CP induced negative effects. Conclusion This study provides a basis for the potential use of EMD in counteracting chemotherapy induced testicular toxicity. The results further suggest that EMD testicular protective effects in CP-treated rats may be mediated through its modulatory role on oxidative stress and inflammation.

Asperuloside attenuates cadmium-induced toxicity by inhibiting oxidative stress, inflammation, fibrosis and apoptosis in rats

“…Mitigating the adverse toxicity of Cd is quite challenging due to the possible risk of toxicity progression involved in approaches like chelation therapy 9 . However, in recent years the antioxidant therapy has gain enormous attention in the prevention or treatment of drug/metal induced organ toxicity due to their inhibitory role on oxidative stress and inflammation 8,10,11 . Since the disruption in the oxidants and antioxidants balance as well as induction of inflammatory responses is a major mechanism involved in Cd-induced toxicity, the elimination of oxido-inflammation may be a viable therapeutic strategy to mitigate Cd toxicity.Asperuloside (ASP) is an iridoid glycoside found in Rubiaceae plants and it has been reported to display intense anti-inflammatory, anticancer, antiobesity and antioxidant properties 12,13 .…”

Testicular niche repair after gonadotoxic treatments: Current knowledge and future directions

“…Different chemotherapy drugs show varying degrees of gonadotoxicity (Silvestris et al., 2020). Cyclophosphamide, a commonly used chemotherapy drug, can cause damage to the DNA in germ cells and interfere with their proliferation, leading to decreased sperm production and infertility (Ghobadi et al., 2017; Wang et al., 2021). Cisplatin, another chemotherapy drug, can cause damage to the Leydig cells in the testes, leading to decreased testosterone production and potential testicular atrophy (Howell & Shalet, 1998; Yucel et al., 2019).…”

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Exhibits Antioxidant Mechanism for Abrogation of Cyclophosphamide-Induced Cardiac Damage and Oxidative Hepatorenal Toxicity in Rats

“…It is a cytotoxic alkylating agent first synthesized in 1958 for interacting with DNA and blocking DNA replication in rapidly dividing cancer cells. Unfortunately, the anticancer cytotoxic effect of CYP is not selective for cancer cells only; it affects healthy tissues and thus the prolong use of CYP has been associated with various organ toxicity [2]. The hepatic metabolites of CYP, acrolein and phosphoramide, are essentially known to incite bladder hemorrhagic cystitis and the antitumor efficacy, respectively [3,4].…”