Oral Nigella sativa oil and thymoquinone administration ameliorates the effect of long-term cisplatin treatment on the enzymes of carbohydrate metabolism, brush border membrane, and antioxidant defense in rat intestine

Abstract

We have previously shown that oral administration of Nigella sativa oil (NSO) ameliorates the deleterious gastrointestinal effects of cisplatin (CP), administered as a single dose. Since a typical clinical CP dosing regimen involves multiple cycles of CP administration in lower doses, in the present study we investigate the protective efficacy of NSO and its major bioactive constituent, thymoquinone (TQ), against multiple-dose CP treatment-induced deleterious biochemical and histological changes in rat intestine. Rats were divided into six groups, viz., control, CP, CP+NSO, CP+TQ, NSO, and TQ. Animals in CP+NSO and CP+TQ groups were pre-administered NSO (2 ml/kg bwt, orally) and TQ (1.5 mg/kg bwt, orally), respectively, daily for 14 days and were then treated with five repeated doses of CP (3 mg/kg bwt, i.p.), every fourth day for 20 days while still receiving NSO/TQ. CP treatment alone led to a significant decline in specific activities of brush border membrane (BBM) enzymes while NSO or TQ administration to CP-treated rats significantly prevented the decline in BBM enzyme activities in the isolated brush border membrane vesicles (BBMV) as well as in mucosal homogenates. Furthermore, both NSO and TQ administration markedly ameliorated CP-induced alterations on carbohydrate metabolism enzymes and the enzymatic and non-enzymatic parameters of antioxidant defense system in the intestinal mucosa. However, NSO appeared to be more efficacious than TQ in protecting against CP-induced gastrointestinal dysfunction. Histopathological findings corroborated the biochemical results. Thus, NSO and TQ may prove clinically useful in amelioration of the intestinal toxicity associated with long-term CP chemotherapy.

Potential synergistic antioxidant effect of thymoquinone and vitamin E on cisplatin-induced acute nephropathy in rats

“…On the other hand, treating the cisplatin administered rats with TQ, Vit E and their combination in G3, G4 and G5, respectively ameliorated the levels of all antioxidants by increasing the activity of catalase and glutathione peroxidase and the levels of reduced glutathione, and decreasing lipid peroxidation which is consistent with Sayed [11] and Shahid et al [9].…”

“…Prevention of the side effects of cisplatin is one of the major issues in treating cancer patients [9,10] and so various methods have been tested to prevent these side effects of cisplatin, such as combined use of free radical scavengers [6,7]. Therefore, the present study was designed to elucidate the availability of using some types of antioxidants of natural sources to alleviate these side effects upon cisplatin treatment [9,10]. In this study, TQ and Vit E were used either separately or in their combination form to declare their role in ameliorating the adverse effects of cisplatin induced nephropathy and hepatotoxicity.…”

“…Thymoquinone (the main constituent of Nigella sativa seed volatile oil) possesses strong antioxidant properties that protect against oxidative damage resulting from free radical-generating agents [8]. It was reported to have anti-inflammatory actions, an analgesic and a protective effect against chemical induced carcinogenesis [9,10]. Thymoquinone also have a protective effect against diabetic nephropathy [11].…”

Thymoquinone therapy remediates elevated brain tissue inflammatory mediators induced by chronic administration of food preservatives

“…The human diet is an crucial component for safeguarding against the upgrowth of cancers. Some new trends in cancer chemotherapy recommended the use of some natural products 7 . One important natural product is Nigella sativa oil, frequently recognized as black cumin.…”

“…This volatile oil is reported to include 30–48% thymoquinone (TQ), the main active ingredient 8,9 . TQ is important in relieving oxidative stress, improve the neuronal survival and therapeutic effects for the treatment of central nervous system tumors 7,10,11 . Oxidative stress was blamed for the harmful effects of higher concentrations of sodium nitrite 12 .…”