Antitumor activity and antioxident role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice

AIM: To study the enzyme activity of CYP2C18 variant with exon 5 skipped. METHODS: A full length CYP2C18 cDNA X1 and an exon 5 skipped variant CYP2C18 X2 were separately subcloned into mammalian expression vector pREP9 to transfect HepG2 cells. The expression of CYP2C18 mRNA in transgenic cells and human liver tissues were determined by RT-PCR. The enzyme activity of CYP2C18 to oxidate tolbutamide in postmitochondrial supernate (S9) fraction was determined by HPLC. The cytotoxicity of ifosfamide to transgenic cells was evaluated by MTT test. RESULTS: HepG2-CYP2C18 X1 cells showed strong expression of the full length CYP2C18 mRNA. On the other hand, HepG2-CYP2C18 X2 cells had only infinitesimal expression of the exon-skipped CYP2C18 as well as the full length CYP2C18, while non-transfected HepG2 cell only demonstrated an infinitesimal expression of the full length CYP2C18. The expression of CYP2C18 exons 2 to 7 was also analyzed by RT-PCR in 7 extratumoral liver tissues. Among them, 3 samples expressed on     

Influence of phenylhydrazine on the antioxidant system of the erythrocytes and the liver in mice

Phenylhydrazine when injected into the mouse acts in two phases. At an early stage it provokes directly in the erythrocytes as well as in the liver a decrease in the concentration of acidosoluble nonprotein thiol groups. Indirectly it causes a later and more lasting increase in glutathione S-transferase and glucose-6-phosphate dehydrogenase activities in the erythrocytes, due mostly to a renewal of the population of these cells, and in glucose-6-phosphate dehydrogenase activity in the liver due to a decrease in hepatic glutathione. Thus, modifications in the erythrocytes are mainly due first to a strong oxidation of hemoglobin and afterwards to the renewal of the population. In the liver, modifications are mostly induced by consumption of reduced glutathione and secondary activation of the pentose cycle. It is suggested that there is a similarity between this chemical aggression and an inflammatory process.     

Protective effect of S-allylcysteine against cyclophosphamide-induced bladder hemorrhagic cystitis in mice

S-Allylcysteine (SAC), an organosulfur compound of aged garlic extract (AGE) regulates the thiol status of the cell and scavenges free radicals. Depletion of thiols along with free radical generation has been implicated in cyclophosphamide (CP)-induced urotoxicity. We studied modulatory effect of SAC on CP-induced urotoxicity in mice focusing on hemorrhagic cystitis (HC). SAC (150 and 300 mg kg⁻¹) was administered in CP treated animals (200 mg kg⁻¹) and bladder was observed for histological and biochemical changes. CP treatment caused a marked increase in the lumen exudates, edema, vasodilation and HC in lamina propia in the bladder. These changes were accompanied by increase in lipid peroxidation (LPO), and decrease in reduced glutathione (GSH) and activities of antioxidant enzymes. SAC not only showed protection in tissue histology but also improved the decreased activities of antioxidant enzymes. SAC treatment also reduced LPO and increased GSH levels. Although SAC treatment did not ensure full recovery, the marked improvement in histology and antioxidants of bladder suggests that it has a significant modulatory effect on CP-induced urotoxicity. Since decrease in antioxidant level is the major cause of CP urotoxicity, the protective effect of SAC deserves its further exploration involving laboratory and clinical investigations.     

Inhibitory effects of methanol extract of plum (Prunus salicina L., cv. ‘Soldam’) fruits against benzo(α)pyrene-induced toxicity in mice

This study was carried out to investigate the chemopreventive effects of immature plum extracts. The methanol extract of immature plums (plum 1), that are picked at 20–40 days before final harvest, has remarkably inhibited the growth of hepatoma HepG2 cells. The effects of immature plum extracts on hepatotoxicity in benzo(α)pyrene (B(α)P, carcinogen)-treated mice were investigated. Male ICR mice were pretreated with immature plum extracts (2.5 or 5 g/kg bw/day, for 5 days, i.p.) before treatment with B(α)P(0.5 mg/kg bw, i.p., single dose). The activities of serum aminotransferase, cytochrome P450 (CYPs) and the hepatic content of lipid peroxide were increased on B(α)P-treatment group than control, but those levels were significantly decreased by the pretreatment of immature plum extracts. The primary CYPs involved in the metabolism and bioactivation of B(α)P are CYP1A1. The pretreatment of immature plum extracts inhibited the induction of CYP1A1 expression. The activities of glutathione peroxidase, superoxide dismutase and catalase were decreased by the pretreatment of immature plum extracts more than with B(α)P alone. Whereas, the hepatic content of glutathione and glutathione S-transferase activity depleted by B(α)P was significantly increased (p > 0.05). These results suggest that immature plum extracts may counteract toxic effects of carcinogens, such as B(α)P, and therefore possess the chemopreventive efficacy.     

Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system.