Piptandenia Africana and Nauclea latifolia protects against Diethylnitrosamine induced hepatic tumors in Albino Wistar rats
Piptandenia africana (PA) and Nauclea latifolia (NL) showed anti-proliferative effects on Hela, MCF7 and ICMST-6 cells. We examined the effect of NL and PA as phytotherapeutic candidates against N-nitrosodiethylamine (DEN)-induced hepatic toxicities and tumorigenesis.
Wistar’s rat were treated as follows: (1)Control, (2)DEN, (3)PA, (4)NL, (5)PA+NL, (6)DEN+ PA, (7)DEN+ NL, (8)DEN+PA+NL. Hepatic transaminases were assessed in serum for hepatoxicity, in addition to bilirubin, blood glucose levels and hepatic antioxidants status. Furthermore, DEN-induced tumors were estimated, and sectioned for histopathological examination.
Animals treated with DEN only, had mean tumor of five (T5), these were reduced to T2, T2 and T1.75 in groups VI, VII and VIII respectively. Blood glucose levels in DEN treated rats were lowest (87.5 ± 5.1) compared to other treated rats.
Elevated markers of oxidative stress and lower antioxidant profile, suggests that group 2 animals were stressed oxidatively compared to other groups. Significantly higher markers of hepatic toxicity indicated DEN injuriousness was highest in DEN only treated animals. Limited histopathology indicated severe mononuclear cells infiltration of the portal triad, and multiple foci of hepatic necrosis in group 2 animals, compared to control. PA, SL and in combination treated animals were devoid of these pathological hallmarks emblematic in DEN treated animals.
Corroborating In vitro findings, treatment with PA and NL mitigated DEN-induced hepatic tumorigenesis. This phytoprotective capacity unveiled, maybe pertinent in averting hepatic damage from potential chemical carcinogens. Elucidating the phytochemistry and mechanisms of PA and NL mode of action is necessary, which could serve as potential anti-tumor drug candidate
Asase A. O-FK, Ekpe K.P. . 2009. Ekpe Impact of cocoa farming on vegetation in an agricultural landscape in Ghana Afr. J. Ecol.
Benoit-Vical F, Valentin A, Cournac V, Pelissier Y, Mallie M, Bastide JM. 1998. In vitro antiplasmodial activity of stem and root extracts of Nauclea latifolia S.M. (Rubiaceae). J Ethnopharmacol 61(3):173-8.
Beutler E, Blume KG, Kaplan JC, Lohr GW, Ramot B, Valentine WN. 1977. International Committee for Standardization in Haematology: recommended methods for red-cell enzyme analysis. Br J Haematol 35(2):331-40.
Bhosale P ML, Ignle AD, Gadre RV, Rao KVK 2002. Protective effect of Rhodotorula glutinisNCIM3353 on the development of hepatic preneoplastic lesions. . Curr. Sci 83(3):303 - 308.
Blois MS. Antioxidant determination by the use of a stable free radical. Nature 181:1199 - 1200.
Cardin R, Piciocchi M, Bortolami M, Kotsafti A, Barzon L, Lavezzo E, Sinigaglia A, Rodriguez-Castro KI, Rugge M, Farinati F. 2014. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway. World J Gastroenterol 20(12):3078-86.
Chuang SE, Cheng AL, Lin JK, Kuo ML. 2000. Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. Food Chem Toxicol 38(11):991-5.
Colagrande S, Inghilesi AL, Aburas S, Taliani GG, Nardi C, Marra F. 2016. Challenges of advanced hepatocellular carcinoma. World J Gastroenterol 22(34):7645-59.
David SP, Munafo MR, Johansen-Berg H, Smith SM, Rogers RD, Matthews PM, Walton RT. 2005. Ventral striatum/nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers: a functional magnetic resonance imaging study. Biol Psychiatry 58(6):488-94.
Devic S. 2016. Warburg Effect - a Consequence or the Cause of Carcinogenesis? J Cancer 7(7):817-22.
Diaz-Gonzalez A, Forner A, Rodriguez de Lope C, Varela M. 2016. New challenges in clinical research on hepatocellular carcinoma. Rev Esp Enferm Dig 108(8):485-93.
Gatenby RA, Gillies, R.J. 2004. Why do cancers have high aerobic glycolysis? Nat Rev Canc 4:891 - 899.
Hajdu SI. 2016. Pathfinders in oncology from ancient times to the end of the Middle Ages. Cancer 122(11):1638-46.
Hanasaki Y, Ogawa S, Fukui S. 1994. The correlation between active oxygens scavenging and antioxidative effects of flavonoids. Free Radic Biol Med 16(6):845-50.
Heindryckx F, Colle I, Van Vlierberghe H. 2009. Experimental mouse models for hepatocellular carcinoma research. Int J Exp Pathol 90(4):367-86.
Heinemann G, Vogt W. 1988. The determination of bilirubin with a new enzymatic method (Dri-STAT bilirubin) using the Hitachi 704 selective analyzer. J Clin Chem Clin Biochem 26(6):391-7.
Huo X, Liu C, Gao L, Xu X, Zhu N, Cao L. 2017. Hepatoprotective Effect of Aqueous Extract from the Seeds of Orychophragmus violaceus against Liver Injury in Mice and HepG2 Cells. Int J Mol Sci 18(6).
Jaradat NA, Al-Ramahi R, Zaid AN, Ayesh OI, Eid AM. 2016. Ethnopharmacological survey of herbal remedies used for treatment of various types of cancer and their methods of preparations in the West Bank-Palestine. BMC Complement Altern Med 16:93.
Kawanishi S, Hiraku Y, Murata M, Oikawa S. 2002. The role of metals in site-specific DNA damage with reference to carcinogenesis. Free Radic Biol Med 32(9):822-32.
Kolaja KL, Klaunig JE. 1997. Vitamin E modulation of hepatic focal lesion growth in mice. Toxicol Appl Pharmacol 143(2):380-7.
Kyriazis AP, Koka M, Vesselinovitch SD. 1974. Metastatic rate of liver tumors induced by diethylnitrosamine in mice. Cancer Res 34(11):2881-6.
Le Lay S, Simard G, Martinez MC, Andriantsitohaina R. 2014. Oxidative stress and metabolic pathologies: from an adipocentric point of view. Oxid Med Cell Longev 2014:908539.
Misra HP, Fridovich I. 1972. The univalent reduction of oxygen by reduced flavins and quinones. J Biol Chem 247(1):188-92.
Najm I, Trussel, R.R. 2001. NDMA Formation in Water & Wastewater. J. Am. Water Works Assoc 93:92-98.
Navarro VJ, and J. R. Senior. 2006. Drug-related hepatotoxicity. N Engl J Med 354(7):731 - 9.
Nermin A.H. Sadik SAE-M, Manal F. Ismail. 2008. Diethylnitrosamine-induced hepatocarcinogenesis in rats: possible chemoprevention by blueberries. African Journal of Biochemistry Research 2(3):081 -087.
Nicholson AB, Watson GR, Derry S, Wiffen PJ. 2017. Methadone for cancer pain. Cochrane Database Syst Rev 2:CD003971.
Owumi SE, O. A. Odunola, and M. Aliyu. 2012. Co-administration of sodium arsenite and ethanol: Protection by aqueous extract of Aframomum longiscapum seeds. Pharmacognosy Res 4(3):154 - 60.
Phillipson JD. 1994. Natural products as drugs. Trans R Soc Trop Med Hyg 88 Suppl 1:S17-9.
Phillipson JD, Wright CW. 1991. Can ethnopharmacology contribute to the development of antimalarial agents? J Ethnopharmacol 32(1-3):155-65.
Pinato DJ, Dalla Pria A, Sharma R, Bower M. 2017. Hepatocellular carcinoma: an evolving challenge in viral hepatitis and HIV coinfection. AIDS 31(5):603-611.
Pirone C, Quirke JM, Priestap HA, Lee DW. 2009. Animal pigment bilirubin discovered in plants. J Am Chem Soc 131(8):2830.
Pitot HC, Dragan YP. 1994. The multistage nature of chemically induced hepatocarcinogenesis in the rat. Drug Metab Rev 26(1-2):209-20.
Qi Y, Chen X, Chan CY, Li D, Yuan C, Yu F, Lin MC, Yew DT, Kung HF, Lai L. 2008. Two-dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma. Int J Cancer 122(12):2682-8.
R. L. 1969. Manuel de Botanique Forestière de l'Afrique Tropicale. IIA. Paris 6e, France: Imprimerie Jouve; 1969. Phytochemistry 3:465-467.
Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28(1):56-63.
Rezaie A, Fazlara A, Haghi Karamolah M, Shahriari A, Najaf Zadeh H, Pashmforosh M. 2013. Effects of Echinacea purpurea on Hepatic and Renal Toxicity Induced by Diethylnitrosamine in Rats. Jundishapur J Nat Pharm Prod 8(2):60-4.
Rotruck JT, Pope AL, Ganther HE, Hoekstra WG. 1972. Prevention of oxidative damage to rat erythrocytes by dietary selenium. J Nutr 102(5):689-96.
Rui W, Xie L, Liu X, He S, Wu C, Zhang X, Zhang L, Yang Y. 2014. Compound Astragalus and Salvia miltiorrhiza extract suppresses hepatocellular carcinoma progression by inhibiting fibrosis and PAI-1 mRNA transcription. J Ethnopharmacol 151(1):198-209.
Shahidi F, and P. K. Wanasundara. 1992. Phenolic antioxidants. Crit Rev Food Sci Nutr 32(1):67 - 103.
Surh YJ, Kundu JK, Na HK, Lee JS. 2005. Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr 135(12 Suppl):2993S-3001S.
Takaki A, Yamamoto K. 2015. Control of oxidative stress in hepatocellular carcinoma: Helpful or harmful? World J Hepatol 7(7):968-79.
Thangapazham RL, Sharma A, Maheshwari RK. 2006. Multiple molecular targets in cancer chemoprevention by curcumin. AAPS J 8(3):E443-9.
Tharappel JC, Lehmler HJ, Srinivasan C, Robertson LW, Spear BT, Glauert HP. 2008. Effect of antioxidant phytochemicals on the hepatic tumor promoting activity of 3,3',4,4'-tetrachlorobiphenyl (PCB-77). Food Chem Toxicol 46(11):3467-74.
Thirunavukkarasu C, Babu E, Ebrahim AS, Chandramohan N, Sakthisekaran D. 2004. Antioxidant-associated chemoprevention by sodium selenite in N-nitrosodiethylamine-induced and phenobarbital-promoted hepatocarcinogenesis in rats. Cell Biochem Funct 22(4):265-71.
Trease GE, Evans, W.C. 2009. Trease and Evans Pharmacognosy: Saunders Ltd. 616 p.
Tremellen K. 2008. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update 14(3):243-58.
Verna L, Whysner J, Williams GM. 1996. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther 71(1-2):57-81.
Vesselinovitch SD, Mihailovich N. 1983. Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res 43(9):4253-9.
Wargovich MJ. 2001. Herbals and cancer. Adv Exp Med Biol 492:195-202.
Wargovich MJ, Woods C, Hollis DM, Zander ME. 2001. Herbals, cancer prevention and health. J Nutr 131(11 Suppl):3034S-6S.