Protective Effects of Kolaviron against Phenylhydrazine-Induced Hepatotoxicity, Genotoxicity, and Splenic Pathology in Wistar Rats
DOI:
https://doi.org/10.54548/Sammendrag
Phenylhydrazine (PHZ) triggers oxidative stress through the generation of reactive oxygen species and lipid peroxidation, resulting in organ and DNA damage. Kolaviron (KV), a biflavonoid complex extracted from Garcinia kola seeds, has shown properties that combat oxidative stress and protect cells. Aim was to evaluate the protective effects of kolaviron against phenylhydrazine-induced hepatotoxicity, splenic pathology, and genotoxicity in Wistar rats. Twenty-eight male rats were divided into four groups: Control (distilled water), PHZ (40 mg/kg intraperitoneally for 3 days), PHZ+KV (PHZ at 40 mg/kg+KV at 100 mg/kg orally for 14 days), and KV alone (100 mg/kg orally for 14 days). Hepatotoxicity, splenic pathology, and genotoxicity were assessed via biochemical analyses, oxidative stress markers, antioxidant parameters, histopathology, and micronucleus testing in bone marrow cells. Results showed PHZ significantly elevated liver enzymes (p<0.05), increased malondialdehyde levels, decreased antioxidant enzymes, and caused periportal fibrosis. Treatment with KV normalized these liver parameters and mitigated histopathological damage. In the spleen, PHZ induced lymphoid follicular hyperplasia, whereas in the PHZ+KV group, we observed lymphoid follicular necrosis; nonetheless, splenic oxidative stress and antioxidant levels remained similar across all groups. For genotoxicity, PHZ significantly increased micronucleated polychromatic erythrocytes and reduced the polychromatic erythrocytes/normochromatic erythrocytes ratio (p<0.05), while KV treatment restored these to near-control levels. Kolaviron showed significant hepatoprotective and genoprotective effects against PHZ-induced toxicity, primarily through modulation of oxidative stress parameters, though its impact on splenic pathology was weak. Further research should investigate the best dosing regimens and molecular mechanisms underlying KV's protective effects against oxidative damage.
Keywords: Kolaviron, Phenylhydrazine, Hepatotoxicity, Genotoxicity, Oxidative stress, splenic pathology
Referanser
1) Akintonwa, A. and Essien, A. R. (1990) 'Protective effects of Garcinia kola seed extract against paracetamol-induced hepatotoxicity in rats', J. Ethnopharmacol. 29: 207 - 211.
2) Alabi, Q. K. and Akomolafe, R. O. (2020) 'Kolaviron diminishes diclofenac-induced liver and kidney toxicity in Wistar rats via suppressing inflammatory events, upregulating antioxidant defenses, and improving hematological indices', Dose-Response 18: 1559325819899256.
3) Andrade, R. J., Chalasani, N., Björnsson, E. S., Suzuki, A., Kullak-Ublick, G. A., Watkins, P. B., Devarbhavi, H., Merz, M., Lucena, M. I., Kaplowitz, N. and Aithal, G. P. (2019) 'Drug-induced liver injury', Nat. Rev. Dis. Primers 5: 58.
4) Ayepola, O. R., Chegou, N. N., Brooks, N. L. and Oguntibeju, O. O. (2013) 'Kolaviron, a Garcinia biflavonoid complex ameliorates hyperglycemia-mediated hepatic injury in rats via suppression of inflammatory responses', BMC Complement. Altern. Med. 13: 363.
5) Beutler, E. and Mary, K. Y. (1963) 'Erythrocyte glutathione reductase', Blood 21: 573 - 585.
6) Björnsson, E. S. (2016) 'Hepatotoxicity by drugs: the most common implicated agents', Int. J. Mol. Sci. 17: 224.
7) Cichoż-Lach, H. and Michalak, A. (2014) 'Oxidative stress as a crucial factor in liver diseases', World J. Gastroenterol. 20: 8082.
8) Ellman, G. L. (1959) 'Tissue sulfhydryl groups', Arch. Biochem. Biophys. 82: 70 - 77.
9) Elmore, S. A. (2006) 'Enhanced histopathology of the spleen', Toxicol. Pathol. 34: 648 - 655.
10) Erukainure, O. L., Salau, V. F., Chukwuma, C. I. and Islam, M. S. (2021) 'Kolaviron: a biflavonoid with numerous health benefits', Curr. Pharm. Des. 27: 490 - 504.
11) Farombi, E. O. (2000) 'Mechanisms for the hepatoprotective action of kolaviron: studies on hepatic enzymes, microsomal lipids and lipid peroxidation in carbontetrachloride-treated rats', Pharmacol. Res. 42: 75 - 80.
12) Farombi, E. O., Adedara, I. A., Ajayi, B. O., Ayepola, O. R. and Egbeme, E. E. (2013) 'Kolaviron, a natural antioxidant and anti-inflammatory phytochemical prevents dextran sulphate sodium-induced colitis in rats', Basic Clin. Pharmacol. Toxicol. 113: 49 - 55.
13) Farombi, E. O., Shrotriya, S. and Surh, Y. J. (2009) 'Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-κB and AP-1', Life Sci. 84: 149 - 155.
14) Farombi, E. O., Tahnteng, J. G., Agboola, A. O., Nwankwo, J. O. and Emerole, G. O. (2000) 'Chemoprevention of 2-acetylaminofluorene-induced hepatotoxicity and lipid peroxidation in rats by kolaviron—a Garcinia kola seed extract', Food Chem. Toxicol. 38: 535 - 541.
15) Gu, X. and Manautou, J. E. (2012) 'Molecular mechanisms underlying chemical liver injury', Expert Rev. Mol. Med. 14: e4.
16) Habig, W. H., Pabst, M. J. and Jakoby, W. B. (1974) 'Glutathione S-transferases: the first enzymatic step in mercapturic acid formation', J. Biol. Chem. 249: 7130 - 7139.
17) Innih, S. O., Omage, S. O. and Omage, K. (2020) 'Hematinic effects of Spondias mombin and its protective role against the spleenotoxic effect of phenylhydrazine', Clin. Phytosci. 6: 80.
18) Liezmann, C., Stock, D. and Peters, E. M. (2012) 'Stress induced neuroendocrine-immune plasticity: A role for the spleen in peripheral inflammatory disease and inflammaging?', Dermatoendocrinol. 4: 271 - 279.
19) Misra, H. P. and Fridovich, I. (1976) 'The oxidation of phenylhydrazine: superoxide and mechanism', Biochemistry 15: 681 - 687.
20) Obayuwana, E. and Obayuwana, M. O. (2022) 'Ameliorative effects of aqueous extract of Brassica nigra on phenylhydrazine-induced liver toxicity in Wistar rats', J. Appl. Sci. Environ. Manage. 26: 661 - 666.
21) Odi, P. A., Udi, O. A., Chris-Ozoko, L. E. and Oyovwi, M. O. (2022) 'Mature Wistar Rats' Spleen and Liver Histomorphological Changes Related to the Duration of Atrazine Exposure', Asian J. Res. Med. Pharm. Sci. 11: 73 - 78.
22) Ola, O. S. and Adewole, K. E. (2021) 'Anticlastogenic and hepatoprotective effects of Kolaviron on sodium valproate-induced oxidative toxicity in Wistar rats', Egypt. J. Basic Appl. Sci. 8: 167 - 179.
23) Ola-Davies, O. E., Ajibade, T. O., Samuel, E. S. and Adedokun, R. A. M. (2019) 'Cytoprotective potential of Spondias mombin fractions on sodium arsenite-induced haematological, biochemical and genotoxic perturbations in rats', Afr. J. Biomed. Res. 22: 315 - 323.
24) Olukanni, A. T., Minari, J. B. and Okpuzor, J. (2023) 'Various parts of Moringa oleifera ameliorate Phenylhydrazine-Induced Spleen toxicity in Male Wistar Rats', Afr. Sci. 24: 4.
25) Pandey, K., Meena, A. K., Jain, A. and Singh, R. K. (2014) 'Molecular mechanism of phenylhydrazine induced haematotoxicity: a review', Am. J. Phytomed. Clin. Ther. 2: 390 - 394.
26) Rungemorris, M., Wu, N. and Novak, R. F. (1994) 'Hydrazine-mediated DNA damage: role of hemoprotein, electron transport, and organic free radicals', Toxicol. Appl. Pharmacol. 125: 123 - 132.
27) Varshney, R. and Kale, R. K. (1990) 'Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes', Int. J. Radiat. Biol. 58: 733 - 743.
28) Wolff, S. P. (1994) 'Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides', Methods Enzymol. 233: 182 - 189.
29) Zangeneh, M. M., Zangeneh, A., Salmani, S., Jamshidpour, R. and Kosari, F. (2019) 'Protection of phenylhydrazine-induced hematotoxicity by aqueous extract of Ocimum basilicum in Wistar male rats', Comp. Clin. Pathol. 28: 331 - 338.
30) Zimmerman, H. J. (1999) Hepatotoxicity: The adverse effects of drugs and other chemicals on the liver (2nd ed.). Lippincott Williams & Wilkins.
Publisert
Utgave
Seksjon
Lisens
Opphavsrett 2025 Nigerian Journal of Physiological Sciences
Dette verket er lisensiert under Creative Commons Attribution 4.0 International License.
