Chrysin abrogates cisplatin-induced oxidative stress, p53 expression, goblet cell disintegration and apoptotic responses in the jejunum of Wistar rats.
Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has pronounced adverse effects, namely nephrotoxicity, ototoxicity, neurotoxicity, hepatotoxicity, diarrhoea and nausea. CDDP-induced emesis and diarrhoea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants, possesses multiple biological activities, such as antioxidant and anti-inflammatory properties. In the present study, we investigated the protective effect of chrysin against CDDP-induced jejunal toxicity. The plausible mechanism of CDDP-induced jejunal toxicity includes oxidative stress, p53 and apoptosis via up-regulating the expression of caspase-6 and -3. Chrysin was administered to Wistar rats orally in maize oil. A single intraperitoneal injection of CDDP was given and the animals were killed after 24 h of CDDP injection. Chrysin ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6-phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin attenuated CDDP-induced goblet cell disintegration, enhanced expression of p53 and apoptotic tissue damage. Histological findings further substantiated the protective effects of chrysin against CDDP-induced damage in the jejunum. The results of the present study demonstrate that oxidative stress and apoptosis are closely associated with CDDP-induced toxicity and chrysin shows the protective efficacy against CDDP-induced jejunum toxicity possibly via attenuating the oxidative stress and apoptotic tissue damage.
Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.
Rehan
R
Khan
Abdul Quaiyoom
AQ
Khan
Wajhul
W
Qamar
Abdul
A
Lateef
Farrah
F
Ali
Muneeb U
MU
Rehman
Mir
M
Tahir
Swati
S
Sharma
Sarwat
S
Sultana
D000818:Animals; D000930:Antidiarrheals / Q000378:metabolism / Q000627:therapeutic use; D000932:Antiemetics / Q000378:metabolism / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000975:Antioxidants / Q000378:metabolism* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D019587:Dietary Supplements; D005419:Flavonoids / Q000378:metabolism* / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000930:Antidiarrheals; D000932:Antiemetics; D000970:Antineoplastic Agents; D000975:Antioxidants; D005419:Flavonoids; D016159:Tumor Suppressor Protein p53; C043561:chrysin; D010088:Oxidoreductases; D005982:Glutathione Transferase; D005978:Glutathione; D002945:Cisplatin