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.

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Abbreviations

ACPase:

Acid phosphatase

ALP:

Alkaline phosphatase

BBM:

Brush border membrane

BBMV:

BBM vesicles

CAT:

Catalase

CP:

Cisplatin

FBPase:

Fructose 1,6-bisphosphatase

G6Pase:

Glucose 6-phosphatase

G6PDH:

Glucose 6-phosphate dehydrogenase

GGTase:

γ-Glutamyl transferase

GR:

Glutathione reductase

GSH:

Glutathione reduced

GSH-Px:

Glutathione peroxidase

GST:

Glutathione S-transferase

HK:

Hexokinase

LAP:

Leucine aminopeptidase

LDH:

Lactate dehydrogenase

LPO:

Lipid peroxidation

MDA:

Malondialdehyde

MDH:

Malate dehydrogenase

ME:

Malic enzyme

NAD:

Nicotinamide adenine dinucleotide

NADH:

Nicotinamide adenine dinucleotide reduced

NADPH:

Nicotinamide adenine dinucleotide phosphate reduced

NADP:

Nicotinamide adenine dinucleotide phosphate

NSO:

Nigella sativa oil

ROS:

Reactive oxygen species

SH:

Sulfhydryl

SOD:

Superoxide dismutase

TCA:

Tricarboxylic acid

TQ:

Thymoquinone

TR:

Thioredoxin reductase

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Acknowledgments

The authors gratefully acknowledge the University Grants Commission (UGC), New Delhi, for the award of Senior Research Fellowship (under MANF scheme) to F.S and Z.F.

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Correspondence to Farah Khan.

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Animal experiments were permitted by the Ministry of Environment, Forests and Climate Change, Government of India, under registration no. 714/GO/Re/02/CPCSEA issued by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) dated 29th October 2014 and approved by the Institutional Animal Ethic Committee (IAEC) of the Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, India.

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The authors declare that they have no conflict of interest.

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Shahid, F., Farooqui, Z., Khan, A.A. et al. 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. Naunyn-Schmiedeberg's Arch Pharmacol 391, 145–157 (2018). https://doi.org/10.1007/s00210-017-1444-6

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Keywords

  • Cisplatin
  • Nigella sativa oil
  • Thymoquinone
  • Gastrointestinal dysfunction
  • Antioxidant parameters