Modulation of Caspase-3 Expression by Arcangelisia flava Post Acetaminophen-Induced Hepatotoxicity in Rat’s Liver
Abstract
BACKGROUND: Acetaminophen, when used at low doses is a safe drug, but at higher doses it induces apoptosis in hepatoma cells. Arcangelisia flava that grows widely in Kalimantan Island, Indonesia, contains berberine which is effective in protecting the liver. This work was aimed to study the effect of A. flava extract on the modulation of caspase-3 in acetaminophen-induced hepatotoxicity.
METHODS: Thirty-five Wistar male rats were divided into groups: I the normal control (water); II the negative control (Arabic gum powder or PGA, 2% in suspension); III the positive control (silymarin); IV-VII (A. flava extract 100, 200, 400, and 800 mg/Kg of body weight (BW), respectively) for 14 days. At day 15th, group II-VII were induced with acetaminophen 1000 mg/Kg of BW per oral for 7 days along with the extracts. At day 22nd, the animals were measured for their serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma-glutamyl transferase (GGT), histological examination, and Western blotting.
RESULTS: Acetaminophen elevated the SGOT and SGPT (3x compared to normal group), and GGT (5x compared to normal group) of the animals in group II. Pre-treatment with higher doses of A. flava extract (group VI and VII) significantly prevented the biochemical changes induced by acetaminophen. Normal histology of the liver was showed by group I, III, VII, whereas dilated sinusoids, central vein (CV) lesion, and local haemorrage were observed in group II, IV, V and VI. Western blotting showed an inhibition of caspase-3 expression by A. flava extract in dose-dependent manner.
CONCLUSION: A. Higher dose A. flava extract shows hepatoprotective activity by preventing the elevation of serum transaminases and transferase levels. Eventually, no damage in the acetaminophen-induced rat’s liver was observed. This plant modulates the expression of caspase 3 protein in dose-dependent manner.
KEYWORDS: Arcangelisia sp, caspase-3, berberine, hepatoprotective activity, NSAIDs, yellow root
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Jaeschke H, McGill MR, Ramachandran A. Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev. 2012; 44: 88-106, CrossRef.
Dong H, Haining RL, Thummel KE, Rettie AE, Nelson SD. Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen. Drug Metab Dispos. 2000; 28: 1397-400, PMID.
Laine JE, Auriola S, Pasanen M, Juvonen RO. Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. Xenobiotica. 2009; 39: 11-21, CrossRef.
LoGuidice A, Boelsterli UA. Acetaminophen overdose-induced liver injury in mice is mediated by peroxynitrite independently of the cyclophilin D-regulated permeability transition. Hepatology. 2011; 54: 969-78, CrossRef.
Boulares AH, Ren T. Mechanism of acetaminophen-induced apoptosis in cultured cells: roles of caspase-3, DNA fragmentation factor, and the Ca2+ and Mg2+ endonuclease DNAS1L3. Basic Clin Pharmacol Toxicol. 2004; 94: 19-29, PMID.
Antoine DJ, Williams DP, Kipar A, Jenkins RE, Regan SL, Sathish JG, et al. High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminopheninduced necrosis and apoptosis in vivo. Toxicol Sci. 2009; 112: 521-31, CrossRef.
Antoine DJ, Williams DP, Kipar A, Laverty H, Park BK. Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity. Mol Med. 2010; 16: 479-90, CrossRef.
Achmadi SS, Batubara I, Sulistiyani. Saponins of albutra (Arcangelisia flava (L.) Merr) as a hepatoprotector. Technical Report. 2006; 2: 20-30, article.
Verpoorte R, Beek TA, Siwon H, Svendsen AB. Studies on Indonesian medicinal plants. Pharmaceutisch Weekblad. 1982; 4: 87-8, CrossRef.
Keawpradub N, Dej-adisai S, Yuenyongsawad S. Antioxidant and cytotoxic activities of Thai medicinal plants named Khaminkhruea: Arcangelisia flava, Coscinium blumeanum and Fibraurea tinctoria. Songklanakarin J Sci Technol. 2005; 27: 456-67, article.
Subeki, Matsuura H, Takahashi K, Yamasaki M, Yamato O, Maede Y, et al. Antibabesial activity of protoberberine alkaloids and 20-hydroxyecdysone from Arcangelisia flava against Babesia gibsoni in culture. J Vet Med Sci. 2005; 67: 223-7, PMID.
Zhao X, Jie Z, Nannan T, Youran C, Yonghuang L. Protective effects of berberine on doxorubicin-induced hepatotoxicity in mice. Biol Pharm Bull. 2012; 35: 796–800, CrossRef.
Feng Y, Siu KY, Ye X, Wang N, Yuen MF, Leung CH, et al. Hepatoprotective effects of berberine on carbon tetrachlorideinduced acute hepatotoxicity in rats. Chin Med. 2010; 5: 33, CrossRef.
Domitrović R, Jakovac H, Blagojević G. Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2, and iNOS expression in CCl(4)-intoxicated mice. Toxicology. 2011; 280: 33-43, CrossRef.
Yu LL, Li RT, Ai YB, Liu W, Deng ZS, Zou ZM. Protoberberine isoquinoline alkaloids from Arcangelisia gusanlung. Molecules. 2014; 19: 13332-41, CrossRef.
Puspitasari E, Pangaribowo DA, Isparnaning IY, Utami Y. Ethanolic extract of Arcangelisia flava leaves is cytotoxic and selective against breast and colon cancer cell lines. Purwokerto: Proceeding of the 1st University of Muhammadiyah Purwokerto-Pharmacy International Conference; 2005. p. 82-6, article.
Maryani, Marsoedi, Nursyam H, Maftuch. The phytochemistry and the anti-bacterial activity of yellow root (Arcangelisia flava Merr.) against aeromonas hydrophila. J Biol Life Sci. 2013; 4 :180-90, article.
Tiwari P, Kumar B, Kaur M, Kaur G, Kaur H. Phytochemical screening and extraction: A review. Internationale Pharmaceutica Sciencia. 2011; 1: 98-106, article.
Hasan MN, Khan RA, Nasiruddin M, Khan AA. Ameliorative effect of Nigella sativa oil against paracetamol-induced hepatic and renal damages in rats. J Pharm Res Int. 2016; 13: 1-10, CrossRef.
Giknis MLA, Clifford CB. Clinical laboratory parameters for Crl: WI (Han). Wilmington: Charles River; 2008.
Hinson JA, Roberts DW, James LP. Mechanisms of acetaminopheninduced liver necrosis. Handb Exp Pharmacol. 2010; 196: 369-405, CrossRef.
Gujral JS, Knight TR, Farhood A, Bajt ML, Jaeschke H. Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis? Toxicol Sci. 2002; 67: 322-8, CrossRef.
Joza N, Kroemer G, Pennigger JM. Genetic analysis of the mammalian cell death machinery. Trends Genet. 2002; 18: 142-9, CrossRef.
Wongbutdee J, Sujarit K, Tuchinda P, Thinapong P, Piyachaturawat P. Hepatoprotective effect of Arcangelisia flava Merr extracts in mice. Thai Journal of Physiological Sciences. 2003; 16: 56.
Fang B, Boross PI, Tozser J, Weber IT. Structural and kinetic analysis of caspase-3 reveals role for s5 binding site in substrate recognition. J Mol Biol. 2006; 360: 654-66, CrossRef.
Yuan HD, Jin GZ, Piao GC. Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice. J Ethnopharmacol. 2010; 127: 528-33, CrossRef.
Pattanayak S, Nayak SS, Panda DR, Dinda SC, Shende V, Javad A. Hepatoprotective activity of crude flavonoids extract of Cajanus scarabaeoides (L) in paracetamol intoxicated albino rats. Asian J Pharm Biol Res. 2011; 1: 22-7.
DOI: https://doi.org/10.18585/inabj.v10i2.412
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