1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital - PubMed (original) (raw)

1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital

Mahendrakumar Chandrasekharappa Banakar et al. World J Gastroenterol. 2004.

Abstract

Aim: To investigate the chemopreventive effects of 1alpha, 25-dihydroxyvitamin D(3) in diethylnitrosamine induced, phenobarbital promoted rat hepatocarcinogenesis.

Methods: The rats were randomly divided into 6 different groups (A-F). Groups A, C and E rats received a single intraperitoneal (i.p.) injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body mass in 9 g/L NaCl solution at 4 wk of age, while group B served as normal vehicle control received normal saline once. After a brief recovery of 2 wk, all the DEN treated rats were given phenobarbital (PB) at 0.5 g/L daily in the basal diet till wk 20. Group A was DEN control. Treatment of 1alpha, 25-(OH)2D3 in group C was started 4 wk prior to DEN injection and continued thereafter till wk 20 at a dose of 0.3 microg/100 microL propylene glycol per one single dose (os) twice a week. Group E received the treatment of 1alpha, 25-(OH)2D3 at the same dose mentioned as above for 15 wk. The rats in group D and F received 1alpha, 25-(OH)2D3 alone as in group C without DEN injection.

Results: The comet assay showed statistically higher mean values for length to width ratios (L: W) of DNA mass and tailed cells (P<0.01; P<0.01 respectively) in DEN treated rats as compared to their normal controls. Continuous supplementation of 1alpha, 25-dihydroxyvitaminD2 showed a significant (P<0.01) decrease in L:W ratio of DNA mass tailed cells. Furthermore, 1alpha, 25-(OH)2D3 supplementations elevated the super oxide dismutase (SOD) activity, hepatic malondialdehyde (MDA) level, reduced glutathione (GSH) and glutathione S-transferase (GST) activity (P<0.01, P<0.05, P<0.05 and P<0.05 respectively). As an endpoint marker histological changes were observed to establish the chemopreventive effects of 1alpha, 25-dihydroxyvitaminD2.

Conclusion: Supplementations of 1alpha, 25-(OH)2D3 has a marked protection against hepatic nodulogenesis, antioxidant enzymes and DNA damages in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.

PubMed Disclaimer

Figures

Figure 1

Basic experimental protocol.

Figure 4

Shows the section of the rat liver (group A) showing abnormal hepatic architecture after a single i.p. Injection of DEN (200 mg/kg b.m.) (HE × 325).

Figure 5

Shows the thin section of normal rat liver untreated (group B) showing hepatocellular architecture (HE × 325).

Figure 6

Shows section of rat liver (group C) initiated with DEN and supplemented with 1α, 25(OH)2D3 [0.3 μg/100 μL propylene glycol per os twice a week for 20 wk] showing almost normal hepatic architecture (HE × 325).

Figure 2

Box-and-whisker plot of the distribution of DNA damage treated with 1alpha, 25(OH)2D3 in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.

Figure 3

Tailed cells (%) in hepatic cells of rats treated with 1alpha, 25(OH)2D3 in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.

Cited by

Potent 19-norvitamin D analogs for prostate and liver cancer therapy.
Kittaka A, Yoshida A, Chiang KC, Takano M, Sawada D, Sakaki T, Chen TC. Kittaka A, et al. Future Med Chem. 2012 Oct;4(16):2049-65. doi: 10.4155/fmc.12.130. Future Med Chem. 2012. PMID: 23157238 Free PMC article. Review.
Vitamin D Mitigates Hepatic Fat Accumulation and Inflammation and Increases SIRT1/AMPK Expression in AML-12 Hepatocytes.
Chang E. Chang E. Molecules. 2024 Mar 21;29(6):1401. doi: 10.3390/molecules29061401. Molecules. 2024. PMID: 38543036 Free PMC article.
Advances in Studies on the Pharmacological Activities of Fucoxanthin.
Xiao H, Zhao J, Fang C, Cao Q, Xing M, Li X, Hou J, Ji A, Song S. Xiao H, et al. Mar Drugs. 2020 Dec 11;18(12):634. doi: 10.3390/md18120634. Mar Drugs. 2020. PMID: 33322296 Free PMC article. Review.
Antiproliferative and Antioxidant Activities of Two Extracts of the Plant Species Euphorbia dendroides L.
Ghout A, Zellagui A, Gherraf N, Demirtas I, Ayse Sahin Y, Boukhenaf M, Lahouel M, Nieto G, Akkal S. Ghout A, et al. Medicines (Basel). 2018 Apr 20;5(2):36. doi: 10.3390/medicines5020036. Medicines (Basel). 2018. PMID: 29677109 Free PMC article.

References

1. Blutt SE, Allegretto EA, Pike JW, Weigel NL. 1,25-dihydroxyvitamin D3 and 9-cis-retinoic acid act synergistically to inhibit the growth of LNCaP prostate cells and cause accumulation of cells in G1. Endocrinology. 1997;138:1491–1497. - PubMed
1. Beaty MM, Lee EY, Glauert HP. Influence of dietary calcium and vitamin D on colon epithelial cell proliferation and 1,2-dimethylhydrazine-induced colon carcinogenesis in rats fed high fat diets. J Nutr. 1993;123:144–152. - PubMed
1. Welsh J. Induction of apoptosis in breast cancer cells in response to vitamin D and antiestrogens. Biochem Cell Biol. 1994;72:537–545. - PubMed
1. Chouvet C, Vicard E, Devonec M, Saez S. 1,25-Dihydroxyvitamin D3 inhibitory effect on the growth of two human breast cancer cell lines (MCF-7, BT-20) J Steroid Biochem. 1986;24:373–376. - PubMed
1. Sardar S, Chakraborty A, Chatterjee M. Comparative effectiveness of vitamin D3 and dietary vitamin E on peroxidation of lipids and enzymes of the hepatic antioxidant system in Sprague--Dawley rats. Int J Vitam Nutr Res. 1996;66:39–45. - PubMed

1alpha, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital - PubMed (original) (raw)