Pharmacological studies on the efficacy of a thymoquinone‐containing novel polyherbal formulation against cisplatin‐induced hepatorenal toxicity in rats

Abstract

The aim of this study was to investigate the protective effect of a novel polyherbal formulation against cisplatin-induced hepatorenal toxicity in six groups of rats. Group I: Normal control; Group II: cisplatin (5 mg/kg i.p.); Group III: cisplatin (5 mg/kg i.p.) + cystone (750 mg/kg p.o.); Group IV: cisplatin + Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone (CFCT) (25 mg/kg p.o.); Group V: cisplatin + CFCT-50; Group VI: cisplatin + CFCT-100. The rats were treated for 4 weeks. Serum and tissue biochemical parameters were assessed. The results showed that aspartate aminotransferase (131.8 IU/L), alanine aminotransferase (66.75 IU/L), alkaline phosphatase (168.67 IU/L), cholesterol (135.15 IU/L), serum urea (56.76 mg/dl), blood urea nitrogen (47.52 mg/dl), and creatinine (3.11 mg/dl) were significantly elevated (p < .001), while total protein (79.02 g/L) was reduced (p < .001) in the cisplatin group. These results were complemented by the outcomes of antioxidant parameters.Finally, CFCT formulation significantly ameliorated cisplatin toxicity. Practical applicationsIn this study, it is revealed that the administration of novel polyherbal formulation (Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone [CFCT]) containing Costus speciosus, Fumaria indica, Cichorium intybus, and thymoquinone ameliorated cisplatin-induced hepatorenal injury in rats. The ameliorative effects against cisplatin toxicity could be via contributing to the antioxidant defense system, by scavenging free radicals and reducing oxidative stress and inflammatory responses. This study aimed at being beneficial to cancer's patients, as they are compelled to take cisplatin, and ultimately suffer from the consequences of irreversible nephrotoxic damage. Furthermore, CFCT formulation could be considered as a dietary supplement for the reduction of cisplatin-induced hepatorenal toxicity in cancer patients on cisplatin treatment. However, further clinical study is necessary.

L-Carnitine Mitigates Oxidative Stress and Disorganization of Cytoskeleton Intermediate Filaments in Cisplatin-Induced Hepato-Renal Toxicity in Rats

“…The histological and immunohistochemical observations of the current study are in harmony and confirmed the alterations of the biochemical and oxidant/antioxidant parameters among the experimental groups. Several histological changes in the liver among CP treated group were noted as recently mentioned by Abuzinadah and Ahmad (2020). The central vein and sinusoidal dilatation and congestion are in accordance with Cagin et al (2015) and Omar et al (2016).…”

“…Cisplatin administration produced a significant decrease in the total proteins and albumin, this result is supported by the result of Abuzinadah and Ahmad (2020) . The above-mentioned results indicate disturbances in protein metabolism induced by CP intoxication due to a reduction in protein synthesis, following liver damage and alteration of functional integrity in the kidney leading to proteinuria, so, their plasma level decreases in hepatotoxic/nephrotoxic conditions ( Sen et al., 2013 ).…”

“…On the other hand, Cayir et al (2009) attributed the hepatotoxicity and nephrotoxicity induced by CP to the free radical generation in the renal and hepatic cells results in lipid peroxidation and oxidative stress that responsible for cellular damage. Cisplatin administration produced a significant decrease in the total proteins and albumin, this result is supported by the result of Abuzinadah and Ahmad (2020). The above-mentioned results indicate disturbances in protein metabolism induced by CP intoxication due to a reduction in protein synthesis, following liver damage and alteration of functional integrity in the kidney leading to proteinuria, so, their plasma level decreases in hepatotoxic/nephrotoxic conditions (Sen et al, 2013).…”

“…(2020) in the liver and kidney tissues, respectively. These results own to oxidative stress that is mediated through the generation of reactive oxygen species (ROS) such as superoxide anion and hydroxyl radical and depletion in plasma antioxidant levels ( Fadl et al., 2019 ; Abuzinadah and Ahmad, 2020 ). So, our results are in harmony with several experimental and clinical studies suggesting that the oxidative stress through the formation of free radicals is one of the mechanisms of CP-induced hepato-renal toxicity ( Ibrahim et al., 2018 ; Neamatallah et al., 2018 ; Abuzinadah and Ahmad, 2020 ).…”

“…Meanwhile, cytokeratins (CKs) represent the largest and most common epithelial IFs (Snider, 2016). Since chemotherapeutic drugs are metabolized by the liver and excreted through the kidneys, hepato-renal toxicity is a common adverse effect caused by chemotherapy (Abuzinadah and Ahmad, 2020).…”