Abstract B45: Piptandenia africana and Nauclea latifolia protect against N-Nitrosodiethylamine induced hepatic tumors in Wistar rats

Abstract

Abstract In vitro studies on crude extracts of Piptandenia africana (PA) and Nauclea latifolia (NL) showed promising anti proliferative effects on Hela, MCF7 and ICMST-6 cell lines. Furtherance to these finding, we examined the anti-tumorigenic effect of NL and PA on N-nitrosodiethylamine (DEN) induced hepatic tumors in Wistar rats as potential phytotherapeutic candidates for cancer prevention and treatment. Five groups of rats (n=5) were co-treated as follows for 60 days: Control (1), DEN only (25μg/g body wt.) (2), DEN+PA (3), DEN+ NL (4) and DEN+PA+NL (5). The serum was assessed for markers of toxicity: alanine and aspartate transaminase (ALT and AST) and alkaline phosphatase (ALP). Total bilirubin (TB) conjugated bilirubin (CB) and creatinine were also examined. Numbers, volumes and sizes of DEN-induced tumors were estimated in harvested livers using a DelcastTM caliper. Sections of liver were examined for histopathological changes and hepatic antioxidants profiles: glutathione peroxide (GPx), superoxide dismutase (SOD), glutathione -s- transferase (GST), catalase and reduced glutathione (GSH). Decreases (p<0.05) in food consumption and body weight were observed in grp 2 rats and had mean tumor of one (T1), in the largest lobe (LL) of their liver. In grp 3, two rats had (T0) but three other rats had (T1) each on the LL of their livers. Grp 4, one rat had (T1) on the LL, while two other rats had (T3) and (T1) on the liver’s smallest lobe (SL). Two rats had (T0), one rat had (T1) on the LL of grp 5 rats, one rat had (T3) on LL and (T2) and (T1) on the intermediate lobe (IL) while the last rat had (T0) on LL and (T1) on SL. Mean blood glucose (±S.D) level in grp2 rats was highest (87.5±5.1) compared to all other treated rats. Hepatic GPx, SOD, GST, catalase and GSH levels suggested that grp2 treated rats had lower levels of antioxidant activities compared to grp 1 and 3. Grp 4 rats exhibited higher antioxidant activity relative to animals in grp 3 and grp 2. In addition markers (AST, ALT and ALP, TB and CB) of hepatotoxicity were highest in grp 4 relative to all other groups. Histopathology of liver sections showed severe portal cellular infiltration by mononuclear cells, congestion and multiple foci of severe hepatic necrosis in grp 2, compared to the grp 1. In contrast grp 3 exhibited mild portal cellular infiltration with moderate Kupffer cell hyperplasia. Grp 4 animals presented with severe but diffuse vacuolar degeneration and necrosis of hepatocytes. Mild portal congestion, occasioned by cellular infiltration by mononuclear cells was observed in grp 5 rats. PA and NL co-treatment mitigated DEN-induced hepatic tumorigenesis in rats. PA and NL exhibited phytotherapuetic properties supporting earlier in vitro findings. This may be relevant in preventing hepatic tumor formation and may serve as potential chemoprevention agents. Elucidating the phytochemistry and mechanistic mode of actions of PA and NL are required. Citation Format: Queen-Esther E. Akinade, Sarah O. Nwozo, Olubunmi A. Akinwumi, Solomon E. Owumi. Piptandenia africana and Nauclea latifolia protect against N-Nitrosodiethylamine induced hepatic tumors in Wistar rats. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B45.