A.R. Rao

Chemopreventive action of garlic on methylcholanthrene-induced carcinogenesis in the uterine cervix of mice

The present paper reports the chemopreventive action of garlic on 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin young adult Swiss albino mice. Insertion of sterile cotton thread impregnated with beeswax containing approximately 600 micrograms of MCA inside the canal of uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experimental cervical carcinogenesis model system, if garlic was administered orally at the dose level of 400 mg/kg body wt./day for 2 weeks before and 4 weeks following carcinogen thread insertion. The cervical carcinoma incidence, as compared with that of the positive control (73%), was 23%. This decline in the incidence of carcinoma was highly significant (P less than 0.01). Hyperplastic and dysplastic changes did not show any definite correlation with the garlic treatment.

Modulatory influence of sandalwood oil on mouse hepatic glutathione S-transferase activity and acid soluble sulphydryl level

The effect of the oil from the wood of Santalum album on glutathione S-transferase (GST) activity and acid soluble sulphydryl (SH) levels in the liver of adult male Swiss albino mice was investigated. Oral feeding by gavage to mice each day with 5 and 15 microliters sandalwood oil for 10 and 20 days exhibited an increase in GST activity in time- and dose-responsive manners. Feeding a dose of 5 microliters sandalwood oil for 10 and 20 days caused, respectively, a 1.80-fold (P < 0.001) and 1.93-fold (P < 0.001) increase in GST enzyme activity, while feeding a dose of 15 microliters of the oil per day for 10 and 20 days induced, respectively, 4.73-fold (P < 0.001) and 6.10-fold (P < 0.001) increases in the enzymes activity. In addition, there were 1.59-fold (P < 0.001) and 1.57 (P < 0.001) increases in acid-soluble SH levels in the hepatic tissue of the mice following feeding of the oil at the dose levels of 5 and 15 microliters for 10 days. Furthermore, mice fed on a diet containing 1% 2(3)-butyl-4-hydroxyanisole (positive control) also showed an increase in hepatic GST activity and SH levels. Enhancement of GST activity and acid-soluble SH levels are suggestive of a possible chemopreventive action of sandalwood oil on carcinogenesis through a blocking mechanism.

Evaluation of the modulatory influence of black pepper (Piper nigrum, L.) on the hepatic detoxication system

The present paper assesses the modifying potential of black pepper on the hepatic biotransformation system in mice. The modulatory effect was assessed on glutathione S-transferase (GST), cytochrome b5 (cyt. b5), cytochrome P-450 (cyt. P-450), acid-soluble sulfhydryl (-SH) content and malondialdehyde (MDA) level. Swiss albino mice of either sex (eight weeks old) were fed on a diet containing 0.5%, 1% and 2% black pepper (w/w) for 10 and 20 days. The findings revealed a significant and dose-dependent increase in GST and -SH content in the experimental groups except the one maintained on 0.5% black pepper diet for 10 days. Elevated levels of cyt. b5 and cyt. P-450 were also statistically significant and dose-dependent. The level of MDA was lowered in the group fed on 2% black pepper diet for 20 days. Being a potential inducer of detoxication system, the possible chemopreventive role of black pepper in chemical carcinogenesis is suggested.

Chemopreventive action of mace (Myristica fragrans, Houtt) on methylcholanthrene-induced carcinogenesis in the uterine cervix in mice

The present paper reports the chemopreventive action of mace (aril covering the testa of the seed of Myristica fragrans) on 3-methylcholanthrene (MCA)-induced carcinogenesis in the uterine cervix of virgin, young adult, Swiss albino mice. Placement of cotton-thread impregnated with beeswax containing MCA (approximately 600 micrograms) inside the canal of the uterine cervix results in the appearance of precancerous and cancerous lesions in the cervical epithelium. In this experiment using the cervical carcinogenesis model system, if mace was administered orally at the dose level of 10 mg/mouse per day for 7 days before and 90 days following carcinogen thread insertion, the cervical carcinoma incidence, as compared with that of the control (73.9%), was 21.4%. This decline in the incidence of carcinoma was highly significant (P less than 0.001). The incidence of precancerous lesions did not display any definite association with different treatments.

Chemopreventive action of mace (Myristica fragrans, Houtt) on DMBA-induced papillomagenesis in the skin of mice

The present paper reports the chemopreventive property of mace (aril covering the seed of Myristica fragrans) on DMBA-induced papillomagenesis in the skin of male Swiss albino mice. When a single topical application of DMBA (150 micrograms in 100 microliters of acetone) was followed, 2 weeks later, by repeated applications of croton oil (1% in acetone, three times/week) skin papillomas appeared in 100% animals and the average tumors per tumor-bearing animal was 5.67. On the other hand, when animals receiving similar treatments were put on a diet containing 1% mace during the periinitiational phase of tumorigenesis, the skin papilloma incidence was reduced to 50% and the average tumor per tumor-bearing mouse was only 1.75. This decline in papilloma was significant (P less than 0.05).

Modulatory influence of camphor on the activities of hepatic carcinogen metabolizing enzymes and the levels of hepatic and extrahepatic reduced glutathione in mice.

The present paper deals with the modulatory influence of camphor on the activities of hepatic phase I and phase II drug metabolising enzymes and the levels of hepatic and extrahepatic reduced glutathione contents in the mouse. Female Swiss albino mice (8-9 weeks old) were treated daily by oral route for 20 days with 50, 150 or 300 mg/kg body weight of camphor dissolved in 0.1 ml of olive oil. Camphor only at the 300 mg/kg body weight dose level caused a significant increase in the activities of cytochrome P450 (P < 0.05), cytochrome b5 (P < 0.05), aryl hydrocarbon hydroxylase (P < 0.05) and glutathione S-transferase (P < 0.05). These modulatory effects were comparable with those induced by 0.75% BHA diet given for 20 days (positive control group). The reduced glutathione level was elevated significantly in liver (P < 0.05) by camphor only at the 300 mg/kg body weight dose level and in liver, lung and stomach (P < 0.05) by BHA.

Modulation of 7,12-Dimethylbenz[a]anthracene-induced Transmammary Carcinogenesis by Disulfiram and Butylated Hydroxyanisole in Mice

The individual as well as combined chemopreventive actions of disulfiram (DSF) and butylated hydroxyanisole (BHA) on 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced transmammary car‐cinogenesis in mice were examined. When nursing mothers receiving normal diet were treated with DMBA (1 mg/mouse) on days 6, 8 and 10 postpartum, the tumor incidence in their 50‐week‐old F1 progeny was 44.1%. When nursing mothers receiving 0.75% BHA diet, 0.5% DSF diet and 0.75% BHA+0.5% DSF diet were similarly treated with DMBA, the tumor incidences in their 50‐week‐old F1 progeny were 14.7% (P<0.05), 12.5% (P<0.05) and 5.8% (P<0.01), respectively. It is concluded that diets containing BHA (0.75%) and DSF (0.5%), singly or in combination, can inhibit trans‐mammary carcinogenesis in Swiss albino mice.

Effect of arecanut, a masticatory, on hepatic drug metabolizing enzymes SH content and lipid peroxidation in lactating mothers and their suckling neonates

The modulation caused by arecanut, a major ingredient of the masticatory substance betel quid, on biotransformation system enzymes, acid soluble sulfhydryl (-SH) content and lipid peroxidation was assessed in lactating mice and their neonates. Following parturition, dams were fed a 1% arecanut diet and F1 mice were nursed by their own mothers during the lactation period of 21 days. Arecanut induced significant increases in the levels of cytochrome b5, cytochrome P-450, glutathione S-transferase and malondialdehyde (MDA) in dams and their pups. However, it decreased the -SH content in lactating mice and F1 progeny; whether the F1 mice were exposed to the translactational dose of arecanut for 21 days or to a similar translactational dose plus a dietary dose of arecanut for additional post weaning period of 21 days, the pattern of changes in the profile of biotransformation system enzymes was essentially similar. The changes elicited by arecanut intake in the levels/activities of enzymes of the biotransformation system, MDA level and -SH content may enhance the susceptibility of neonatal stages of mice to the action of chemical carcinogens.

Modulatory influence of arecanut on antioxidant 2(3)-tert-butyl-4-hydroxy anisole-induced hepatic detoxification system and antioxidant defence mechanism in mice

This paper assesses the modificatory potential of arecanut (Areca catechu L.), a popular masticatory substance, on 2(3)-tert-butyl-4-hydroxy anisole (BHA)-induced changes in the hepatic detoxification system and antioxidant defence mechanisms in mice. The modulatory effects on biochemical parameters including glutathione S-transferase (GST), cytochrome b5, cytochrome P-450, acid soluble sulfhydryl (-SH) content and microsomal lipid peroxidation (MDA) levels were assessed. Mice were fed either a normal diet or diets containing 0.25%, 0.5% or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment the feed was supplemented with 0.5% or 1% BHA. Inclusion of BHA in the diet significantly modulated the detoxification system enzymes, -SH content and malondialdehyde (MDA) levels in the liver of the mice. BHA-induced alterations in hepatic GST and -SH content were depressed while cytochrome b5, cytochrome P-450 and MDA levels were further elevated by the arecanut treatment.

Effect of arecanut on the black mustard (Brassica niger, L.)-modulated detoxication enzymes and sulfhydryl content in the liver of mice

The modulatory potential of arecanut, a popular masticatory, was assessed on the black mustard-induced changes in hepatic detoxication system in mice. The modulatory effect was assessed on glutathione S-transferase (GST), cytochrome b5 (Cyt. b5) and cytochrome P-450 (Cyt. P-450) and acid-soluble sulfhydryl (-SH) content. Mice were fed on either normal diet or diet containing 0.25%, 0.5% or 1% (w/w) arecanut for 45 days. During the last 10 days of treatment the feed was supplemented with 0.5% or 1% black mustard, the popular condiment. Dietary feeding of mustard could significantly enhance the studied phase I and phase II enzymes as well as -SH content in murine liver. However, black mustard-induced alterations in GST and -SH content were lower, while Cyt. b5 and Cyt. P-450 levels were much higher in mice receiving arecanut treatment than controls.