Therapeutic Potential of Capsaicin against Cyclophosphamide-Induced Liver Damage

Abstract

Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1β, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients.

Capsaicin Ameliorates the Cyclophosphamide-Induced Cardiotoxicity by Inhibiting Free Radicals Generation, Inflammatory Cytokines, and Apoptotic Pathway in Rats

“…Positive control: CYC 200 mg/kg, intraperitoneal (i.p) on the 4th day with normal saline [ 28 , 30 , 31 ] (CYC 200 alone).…”

“…It is also high in carotenoids, which have antioxidant effects [ 25 , 26 ]. Caps’ powerful pharmacological effects include analgesic activity, anti-obesity, antipruritic, anti-inflammatory, anti-apoptotic, antineoplastic, free radical scavenging, cardioprotective, hepatoprotective, and neuroprotective actions [ 20 , 21 , 27 , 28 ]. In terms of molecular mechanisms, a wide range of signaling pathways are regulated by Caps treatment, including pro-inflammatory chemicals, such as prostaglandin E2 (PGE2), (IL-6), tumor necrosis factor-alpha (TNFα), and nitric oxide (NO).…”

Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats

“…The isolated heart was properly washed in chilled normal saline before being stored in a 10% buffered neutral formalin solution. The cardiac tissue was then embedded in paraffin [ 32 ] after being fixed. Afterwards, hematoxylin and eosin were used to stain sections of heart tissue (H&E).…”

Sesamin’s Therapeutic Actions on Cyclophosphamide-Induced Hepatotoxicity, Molecular Mechanisms, and Histopathological Characteristics

“…In accordance with standard histology practices, the liver tissue was fixed in 10% formaldehyde before being embedded in paraffin [24]. These implanted samples were sliced to 5 mm thickness by microtome, and they were then fixed on a slide and stained with hematoxylin and eosin (H&E).…”