Abrogation of potassium bromate-induced renal oxidative stress and subsequent cell proliferation response by soy isoflavones in Wistar rats

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this study, we show the modulatory effect of soy isoflavones on KBrO3-mediated renal oxidative stress and subsequent cell proliferation response in Wistar rats. KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, activities of renal anti-oxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H2O2). KBrO3 treatment also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). There was also significant recovery of renal glutathione content (P < 0.01), anti-oxidant enzymes and phase-II metabolising enzymes (P < 0.001). Thus, our results show that soy isoflavones acts as potent chemopreventive agent against KBrO3-mediated renal oxidative stress, toxicity and subsequent cell proliferation response in Wistar rats.     

CHEMOPREVENTIVE EFFECT OF VITIS VINIFERA EXTRACT ON 12-O-TETRADECANOYL-13-PHORBOL ACETATE-INDUCED CUTANEOUS OXIDATIVE STRESS AND TUMOR PROMOTION IN MURINE SKIN

Vitis vinifera (grapes) is used as a fruit worldwide and known for its pharmacological properties. The present paper assesses the chemopreventive potential of Vitis vinifera against 12-O-tetradecanoyl-13-phorbol acetate (TPA)-mediated tumor promotion in 7,12-dimethyl-benz[a]anthracene (DMBA) initiated mice skin. Skin tumor initiation was achieved by a single topical application of DMBA (40 microg/animal/0.20 ml acetone) to mice. Two weeks after the initiation, promoting agent, TPA (5.0 microg/animal/0.2 ml acetone) was applied two times a week for 20 weeks. Pretreatment of Vitis vinifera 1h prior to each application of TPA resulted in protection against cutaneous tumorigenesis in dose-dependent manner. This inhibition was evident when tumor data was considered as the percentage of mice with tumor and the number of tumors per mouse. We have shown that typical application of Vitis vinifera prior to that of TPA resulted in significant inhibition against TPA-caused induction of epidermal ODC activity (P<0.001) and DNA synthesis. Application of Vitis vinifera at a dose level of 5.0 mg and 10.0 mg kg(-1) body weight in acetone prior to that of TPA treatment resulted in partial significant inhibition of oxidative stress in dose-dependent manner. The concomitant increase in the microsomal lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.001). In addition, the depleted level of glutathione and inhibited activities of antioxidant enzymes were recovered to the partial significant level. Hence, it can be suggested that Vitis vinifera can be used as a chemopreventive agent against oxidative stress and carcinogenesis.     

Modification by phenobarbital of decreased glutathione content and glutathione S-transferase activity in livers of lead-treated mice.

Lead acetate (100 mg/kg) administered i.p. to male mice decreased hepatic glutathione (GSH) content and also glutathione S-transferase (GST) activity. However, the liver GSH content of mice treated with both lead and phenobarbital (80 mg/kg, i.p.) remained unchanged, whereas their GST activities were higher than the controls. Phenobarbital antagonized the Pb-induced decrease in liver adenosine triphosphate content. Additionally, phenobarbital shortened the half-life of hepatic GSH determined using buthionine sulfoximine, an inhibitor of GSH synthesis. Acceleration of hepatic GSH turnover by phenobarbital possibly diminishes the Pb-induced impairment of GSH-conjugation of xenobiotics.     

Evaluation of Cissampelos pareira. Against Gastric Cancer and Enzymes Associated with Carcinogen Metabolism

Abstract

The current study is an effort to identify the effect of a hydroalcohol (50% ethanol) extract of roots of Cissampelos pareira. (L.) Hirsuta (Menispermaceae) (CPE) in forestomach cancer and on carcinogen metabolizing phase I and phase II enzymes along with antioxidant enzymes. In forestomach, the activities of glutathione S.-transferase (GST), DT-diaphorase (DTD), and superoxide dismutase (SOD) increased significantly and dose-dependently. The protective effect of CPE was studied against benzo(a.)pyrene [B(a.)P]-induced gastric cancer in mice, and the tumor incidence was reduced and the mean number of tumors and the tumor multiplicity were reduced significantly and dose-dependently. The modulatory effect of CPE was also examined on carcinogen metabolizing phase I and phase II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase, and lipid peroxidation in liver. Significant increases in the levels of acid-soluble sulfhydryl (–SH) and cytochrome P₄₅₀ contents and in enzyme activities of cytochrome P₄₅₀ reductase, cytochrome b₅ reductase, GST, DTD, SOD, catalase, glutathione (GSH) peroxidase, and GSH reductase but decreased malondialdehyde (MDA) were observed. Butylated hydroxyanisole (BHA) showed an increase in hepatic levels of GSH content, cytochrome b₅, DTD, GST, glutathione reductase (GR), and catalase, whereas MDA formation was inhibited significantly. BHA also showed increased levels of DTD, GST, and SOD significantly in forestomach. The enhanced GSH level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of Cissampelos pareira. against chemotoxicity, including carcinogenicity.     

Modulation of cisplatin cytotoxicity and cisplatin-induced DNA cross-links in HepG2 cells by regulation of glutathione-related mechanisms

Glutathione (GSH), glutathione S-transferase (GST), and glutathione conjugate export pump (GS-X pump) have been shown to participate collectively in the detoxification of many anticancer drugs, including cisplatin. Identification and regulation of the rate-limiting step in the overall system for cisplatin detoxification is of crucial importance for sensitization of human tumor cells to cisplatin. In this study, the GSH content, GST activity, and GS-X pump activity were regulated separately to examine effects of the regulation on cisplatin cytotoxicity and cisplatin-induced DNA interstrand cross-links (ICL) in HepG2 cells. Seventy-percent depletion of GSH by buthionine sulfoximine (BSO) and 50% increase of GSH by monoethyl GSH ester (GSHe) potentiated and decreased cisplatin cytotoxicity, respectively. This was reflected by a significant decrease and increase of their respective IC(50) values by 62 and 107%. Cisplatin-induced ICL was also potentiated by depletion of GSH by BSO and decreased by enrichment of GSH by GSHe, as shown by a 125% increase and a 34% decrease of cross-linked DNA compared with control samples exposed to cisplatin alone (p = 0.008 and 0.03, respectively). On the other hand, inhibition of GST and GS-X pump by ethacrynic acid, quercetin, tannic acid, and indomethacin at concentrations that inhibited activities of GST and GS-X pump by more than 50% had no significant effects on cisplatin cytotoxicity and cisplatin-induced DNA ICL in these cells. The results showed that of the parameters measured, intracellular GSH seems to be the rate-limiting factor, and its regulation would provide a more promising strategy for sensitization of human liver tumor cells to cisplatin.     

Nigella sativa (black cumin) ameliorates potassium bromate-induced early events of carcinogenesis: diminution of oxidative stress

Potassium bromate (KBrO3) is a potent nephrotoxic agent. In this paper, we report the chemopreventive effect of Nigella sativa (black cumin) on KBrO3-mediated renal oxidative stress, toxicity and tumor promotion response in rats. KBrO3 (125 mg/kg body weight, intraperitoneally) enhances lipid peroxidation, gamma-glutamyl transpeptidase, hydrogen peroxide and xanthine oxidase with reduction in the activities of renal antioxidant enzymes and renal glutathione content. A marked increase in blood urea nitrogen and serum creatinine has also been observed. KBrO3 treatment also enhances ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into renal DNA. Prophylaxis of rats orally with Nigella sativa extract (50 mg/kg body weight and 100 mg/kg body weight) resulted in a significant decrease in renal microsomal lipid peroxidation (P < 0.001), gamma-glutamyl transpeptidase (P < 0.001), H2O2 (P < 0.001) and xanthine oxidase (P < 0.05). There was significant recovery of renal glutathione content (P < 0.01) and antioxidant enzymes (P < 0.001). There was also reversal in the enhancement of blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Data suggest that Nigella sativa is a potent chemopreventive agent and may suppress KBrO3-mediated renal oxidative stress, toxicity and tumour promotion response in rats.     

Low iron state is associated with reduced tumor promotion in a two-stage mouse skin carcinogenesis model.

The purpose of this study was to investigate the effect of low iron state in a two-stage mouse skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene (DMBA)-initiated and benzoyl peroxide (BPO)-promoted cutaneous tumorigenesis. All mice were treated with DMBA. Low iron state was achieved by injection with phenylhydrazine hydrochloride and feeding low iron diet. A low iron state resulted in a decrease in tumor incidence (papillomas and carcinomas) and number of tumors/mouse. Also, the conversion of papillomas to carcinomas was lower in mice on a low iron state. BPO treatment enhanced epidermal lipid peroxidation (LPO) and was accompanied by a depletion in the level of epidermal reduced glutathione (GSH) and decrease in the activities of antioxidant enzymes. BPO treatment also increased ornithine decarboxylase (ODC) activity and [3H]thymidine incorporation into cutaneous DNA. Mice in a low iron state were less susceptible to the effects of BPO treatment, as was apparent from a partial recovery of GSH levels and the activities of antioxidant enzymes, as well as a lower induction in ODC activity, [3H]thymidine incorporation into cutaneous DNA and lesser epidermal LPO. As expected, cutaneous iron levels were lower in mice on a low iron state. Thus, our data show that the tumor-promoting potential of BPO is reduced by low iron state in a two-stage mouse skin carcinogenesis model.     

Abrogation of DEN/Fe-NTA induced carcinogenic response, oxidative damage and subsequent cell proliferation response by Terminalia chebula in kidney of Wistar rats

In an effort to identify a new chemopreventive agent, the present study was conducted to investigate the role of T. chebula in the prevention of ferric nitrilotriacetic acid (Fe- NTA) induced oxidative stress and renal tumorigenesis in Wistar rats. A single application of Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) significantly induced oxidative stress and elevated the marker parameters of tumor promotion. However, the pretreatment of animals with different doses of T. chebula extract (25 and 50 mg/kg body weight) restored the levels of reduced glutathione (GSH) and cellular protective enzymes (p < 0.05). Concomitantly, malondialdehyde (MDA) formation and hydrogen peroxide content were also reduced significantly (p < 0.05) at both the doses. The promotion parameters tested (ornithine decarboxylase activity and DNA synthesis) were also significantly suppressed (p < 0.05). T. chebula also inhibited N-diethyl nitrosamine initiated renal carcinogenesis by showing reduction in the number of animals with renal cell tumors and percentage incidence of tumor as compared to the DEN initiated and Fe-NTA promoted rats. The study was further histologically confirmed. These results suggest a potential role of T. chebula in protection from Fe-NTA-induced renal carcinogenesis and oxidative damage.     

Comparison of some biochemical properties of epidermis in tumor promotion-susceptible and -resistant strains of mice

It has been reported that CD-1 and SENCAR mice are susceptible and C57BL/6 mice are resistant to skin tumor promotion caused by phorbol esters. Specific binding of a phorbol ester to its epidermal receptor site, epidermal protein kinase C activity, and ornithine decarboxylase (ODC) induction in epidermis were compared between tumor promotion-susceptible and -resistant strains of mice. Specific binding of [3H]12-O-tetradecanoylphorbol-13-acetate (TPA) to the particulate fraction of the epidermis of C57BL/6 mice gave a similar dissociation constant (Kd) and a maximal number of binding sites (Bmax) to those of CD-1 mice. Protein kinase C activity of the epidermal 105,000 xg supernatant was not significantly different between C57BL/6 and CD-1 mice. Protein kinase C activity of the 105,000 xg pellet, however, was significantly higher in C57BL/6 mice than in CD-1 mice. A topical application of TPA to the skin caused epidermal ODC induction in all of these strains of mice. At any doses of TPA, TPA-induced epidermal ODC activity of C57BL/6 mice was always higher than those of SENCAR and CD-1 mice. Maximal induction of epidermal ODC by TPA was also highest in C57BL/6 mice among these three strains of mice. These results indicate that the mechanism of the difference in susceptibility of C57BL/6, CD-1 and SENCAR mice to the tumor-promoting action TPA resides in a step distal to or other than the protein kinase C activation and ODC induction.     

Glutathione and glutathione-related enzymes in colorectal cancer patients

In recent years much attention has been focused on the role of glutathione (GSH) and GSH-related enzymes such as glutathione peroxidase (GSH Px), glutathione reductase (GSH Red), and glutathione S-transferase (GST) in the inhibition of free radical-induced carcinogenesis. In this study, erythrocyte GSH levels and activities of GSH Px, GSH Red, and GST were determined in patients with colorectal tumors (n = 20, mean age 54.5 +/- 8.3 yr). Erythrocyte GSH Red and GST activities were significantly higher in patients with colorectal tumors. Erythrocyte GSH levels and GSH Px activities were found to be significantly decreased in the patients. When the patients were classified based on their clinical grading (Dukes classifications), there was no significant difference in studied parameters between Dukes B and Dukes C. Our results suggest that oxidative stress may play an important role in colorectal tumorigenesis and that these events have no effect on the clinical grading of the colorectal tumor.     

Skin tumorigenic potential of aflatoxin B1 in mice.

Aflatoxin B1 (AFB1) has been classified as a category I human carcinogen, which is responsible for a high incidence of hepatocellular carcinoma. Since exposure to AFB1 can occur through skin contact in addition to ingestion and inhalation, the carcinogenic potential of topically applied AFB1 on mouse skin was investigated. Our results show that single topical application of AFB1 (80 nmol) as a tumor initiator, followed by twice weekly application of 12-tetradecanoyl phorbol myristate acetate (TPA, 4 nmol), resulted in tumor formation after 13 weeks. However, no tumorigenic potential was observed when AFB1 (16 nmol) was used either as a complete carcinogen or as a tumor promoter (4 nmol). Histological analysis of skin showed squamous cell carcinoma in the AFB1/TPA treated group. The application of AFB1 as a complete carcinogen, an initiator or a promoter after 24 weeks demonstrated widespread degenerative and necrotic changes in hepatic tissue as well, suggesting liver to be the target organ following percutaneous absorption. Additionally, twice weekly topical application of AFB1 caused significant induction of cutaneous CYP IA monoxygenases without any effect on hepatic levels while glutathione-S-transferase activity was induced more in the liver than skin. The topical application of AFB1 also resulted in increased hepatic and cutaneous lipid peroxidation with concomitant depletion of glutathione content. It is likely that due to higher induction of hepatic GST activity, products of lipid peroxidation may be detoxified and therefore unable to cause DNA damage making mice resistant to hepatic tumor formation. The overall results indicate a tumor initiating potential of AFB1 in mice and suggest that continued dermal exposure of AFB1, even at low doses, might lead to degenerative changes in hepatocytes.     

Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism

Context: Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions.

Objective: The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model.

Materials and methods: PCOS was induced in Sprague–Dawley rats with of 1?mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100?mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied.

Results: Soy isoflavones (100?mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p?p?p?p?p?Discussion: Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood.

Conclusion: Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.     

Dose, time and route dependency of the induction of rat hepatic ornithine decarboxylase by 12-tetradecanoylphorbol 13-acetate.

Ornithine decarboxylase (ODC) activity, the rate limiting enzyme in polyamine biosynthesis, was determined after 12-O-tetradecanoylphorbol 13-acetate (TPA) administration to female Sprague-Dawley rats. The extent of induction depended on the dose, exposure, time and route of administration. The most effective dose for ODC induction by the intraperitoneal route was 40 ug TPA/kg which caused 3-5 fold ODC induction. Maximal ODC induction occurred in a narrow time band 5 hours after TPA administration. TPA had no adverse effects on hepatic DNA (measured by alkaline elution), cytochrome P-450 content and reduced glutathione content or serum alanine aminotransferase (SGPT) activity.     

Effects of organosulfur compounds from garlic oil on the antioxidation system in rat liver and red blood cells.

The modulation of garlic oil (GO) and three allyl compounds, diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS), on the antioxidation system in rat livers and red blood cells was examined. Rats were orally administered GO (200 mg/kg body weight), DAS (20, 80 mg/kg body weight), DADS (80 mg/kg body weight) or DATS (70 mg/kg body weight) three times a week for 6 weeks. Control rats received corn oil (2 ml/kg body weight) alone. GO, DADS and DATS treatment significantly increased the glutathione (GSH) content (48-84%) in red blood cells (P < 0.05). DATS displayed a greater enhancement than GO and DADS (P < 0.05). Hemolysis induced by tert-butyl hydroperoxide was not suppressed by GO or allyl compound treatment although higher GSH content was evident. Hepatic GSH was not influenced by garlic components. In rat livers, DADS and DATS significantly increased the activity of GSH reductase (46 and 54%, respectively) and of GSH S-transferase (GST) (63 and 103%, respectively), but decreased the GSH peroxidase activity (27 and 28%, respectively). In contrast, GSH reductase and GST activities in the DAS group, either 20 or 80 mg/kg body weight, were similar to the control group. A decrease of GSH peroxidase activity was observed in rats dosed with 80 mg/kg body weight (P < 0.05). An increase in GST activity and a decrease in GSH peroxidase activities were also noted in GO-treated rats (P < 0.05). In red blood cells, three GSH-related antioxidant enzyme activities were not affected by garlic oil and its organosulfur components. Immunoblot assay showed that, accompanying the increase in hepatic GST activity, GO, DADS, DAS (80 mg/kg body weight) and DATS increased the expression of GST Ya, Yb1 and Yc proteins. Results indicate that GO and three allyl compounds play a differential role in modulation of the GSH-related antioxidant system in rat livers and red blood cells.     

Chemomodulatory effect <Emphasis Type="Italic">Melastoma Malabathricum</Emphasis> Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation,oxidative stress,and early markers of tumor expansion

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC–MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (H₂O₂) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-β) and inflammatory mediator (PGE₂). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC–MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.     

In vitro and in vivo evaluation of topical delivery and potential dermal use of soy isoflavones genistein and daidzein

Genistein, daidzein, and glycitein are soy isoflavones. These compounds can be used to protect the skin from oxidative stress induced by UVB radiation. To this end, the feasibility of skin absorption of soy isoflavones was evaluated in the present study. As assayed by flow cytometry, UVB-induced H(2)O(2) production in keratinocytes was inhibited by genistein and daidzein, confirming that these two compounds can act as free radical scavengers when keratinocytes are photodamaged. Glycitein showed no protective activity against photodamage. The effects of vehicles on the in vitro topical delivery from saturated solutions such as aqueous buffers and soybean oil were investigated. The isoflavones in a non-ionized form (pH 6) showed higher skin deposition compared to the ionized form (pH 10.8). Soybean oil reduced the isoflavone amount retained in the skin, especially for genistein. Genistein generally exhibited greater skin absorption than did daidzein. However, daidzein permeation was enhanced when an aglycone mixture was used as the active ingredient. An eutectic effect was proposed as the enhancing mechanism. In vivo skin deposition showed a linear correlation with the in vitro results. The safety profiles suggested no or only negligible stratum corneum disruption and skin erythema by topical application of soy isoflavones. It was concluded that topical delivery may serve as a potent route for soy isoflavones against photoaging and photodamage.     

Influence of silymarin administration on hepatic glutathione-conjugating enzyme system in rats treated with antitubercular drugs

OBJECTIVE: This study evaluated the influence of simultaneous administration of silymarin (SIL), a hepatoprotective and antioxidant agent, on the status of glutathione (GSH) and its metabolising enzymes in the liver tissue of rats treated with antitubercular drugs, i.e. isoniazid (INH), rifampicin (RIF) and pyrazinamide (PYR). METHODS: Male Wistar albino rats (n = 24) were randomly divided into four groups. Group I received saline as they served as controls. Group II rats were administered antitubercular drugs (INH 25 mg/kg + RIF 50 mg/kg + PYR 140 mg/kg orally) daily for 45 days. Group III animals were treated with SIL (50 mg/kg orally) simultaneously with the antitubercular drugs for the same period. Group IV animals were treated with SIL alone. The status of GSH, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-s-transferase (GST) in liver tissue was evaluated at the end of the study. RESULTS: Administration of antitubercular drugs caused a significant decrease (p < 0.001) in the status of GPx, GST and GR and of non-enzymic (GSH) antioxidants in liver tissue when compared with saline-treated control rats. Simultaneous treatment of SIL with antitubercular drugs completely prevented decreases in the levels of all the above parameters. Treatment with SIL alone enhanced the activities of GST (p < 0.001) and GPx (p < 0.05) and did not alter glutathione levels compared with control. CONCLUSION: A fall in the status of glutathione and its conjugating enzymes upon administration of antitubercular drugs denotes an impairment of the antioxidant defence mechanism. Simultaneous administration of SIL afforded complete protection of the liver against this abnormality, an effect that could have been due to the strong antioxidant properties of SIL.     

Effect of elastase in reversing the de-differentiation of rabbit costal chondrocytes in culture induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA).

As elastase is known to affect cell functions in various cell systems, its effects on the functions of control and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated chondrocytes in vitro were examined. Pretreatment of chondrocytes with TPA (10(-8) M) for 48 h significantly enhanced DNA synthesis, inhibited glycosaminoglycan (GAG) synthesis and inhibited the increase in ornithine decarboxylase (ODC) activity in response to parathyroid hormone (PTH) relative to values in control cultures. Addition of elastase (1, 10 and 50 ng/ml) for 24 h partially inhibited the de-differentiated phenotypes induced by TPA such as the decreased synthesis of GAG and decreased response of ODC activity to PTH without affecting the DNA synthesis. Moreover, elastase significantly increased both the basal level of cyclic AMP and that on PTH treatment of TPA-pretreated cells. These results suggested that elastase partially restored the differentiated phenotypes of de-differentiated chondrocytes probably through its effect in increasing the level of intracellular cyclic AMP.     

乙醇摄入对小鼠肝生物转化酶活性及抗氧化功能的影响

观察摄入乙醇（２．５ ｇ·ｋｇ－ １ ｐｏ,每日１ 次）后小鼠肝脏药物代谢酶活性及抗氧化功能的变化,为临床安全用药提供实验依据． 结果表明乙醇摄入４ 周内可诱导苯胺羟化酶,谷胱甘肽Ｓ－转移酶的活性,氨基比林脱甲基酶活性无明显变化,４ 周后则可使上述药酶活性下降,提示长期乙醇摄入对药物代谢的抑制性影响;乙醇摄入早期肝各抗氧化成分无明显改变,４ 周后,谷胱甘肽还原酶,谷胱甘肽过氧化酶,超氧化物歧化酶活性及谷胱甘肽含量逐渐下降,但过氧化氢酶活性明显升高,至第８ 周末下降,谷胱甘肽含量恢复正常,表明乙醇对肝抗氧化功能影响与摄入时间有关．