In vitro antioxidant and in vivo prophylactic effects of two gamma-lactones isolated from Grewia tiliaefolia against hepatotoxicity in carbon tetrachloride intoxicated rats

Grewia tiliaefolia is widely used in traditional Indian medicines to cure jaundice, biliousness, dysentery and the diseases of blood. Bioassay-guided fractionation of methanolic extract of the G. tiliaefolia bark has resulted in the isolation of D-erythro-2-hexenoic acid gamma-lactone (EHGL) and gulonic acid gamma-lactone (GAGL). Hepatoprotective activity of the methanolic extract and the isolated constituents were evaluated against CCl4-induced hepatotoxicity in rats. The treatment with methanolic extract, EHGL and GAGL at oral doses of 100, 150 and 60 mg/kg respectively with concomitant CCl4 intraperitoneal injection (I ml/kg) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase and the incidence of liver necrosis compared with the CCl4-injected group without affecting the concentrations of serum bilirubin and hepatic markers. EHGL and GAGL significantly inhibited the elevated levels of thiobarbituric acid reactive substances and glutathione in liver homogenates. Histology of the liver tissues of the extract and isolated constituents treated groups showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the normal control. The results revealed that the hepatoprotective activity of EHGL is significant as similar to the standard drug silymarin. To clarify the influence of the extract and isolated constituents on the protection of oxidative-hepatic damage, we examined in vitro antioxidant properties of the test compounds. The extract and the constituents showed significant free radical scavenging activity. These results suggest that the extract as well as the constituents could protect the hepatocytes from CCl4-induced liver damage perhaps, by their anti-oxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4, (C) 2009 Elsevier B.V. All rights reserved.

Effect of ICSH on Early Pregnancy in Hypophysectomized Pregnant Rats

Moudgal and co-workers1-3 recently reported that the administration to intact pregnant rats of rabbit antiserum ovine interstitial cell stimulating hormone (ICSH) on any one day between the eighth and twelfth days of pregnancy resulted in resorption of foetuses and termination of pregnancy. This effect was readily reversed by the simultaneous administration of progesterone but not by oestradiol-17β. These observations suggested that ICSH was involved in progesterone synthesis and as such is a luteotropic factor in the rat.

Inhibitory activity of Image -asparaginase from Mycobcacterium tuberculosis on Yoshida ascites sarcoma in rats

The antitumor activity of Image -asparagine amidohydrolases (EC 3.5.1.1) from Mycobacterium tuberculosis H37Rv and H37Ra strains has been tested on Yoshida ascites sarcoma in rats. The enzyme specific to M. tuberculosis H37Ra but not to H37Rv has proved to be effective in inhibiting the growth of the sarcoma. Comparative studies on the activity of this enzyme with that of similar enzyme from Escherichia coli B, has shown that at the same levels the former is more effective than the latter. Long-lived immunity to this tumor in A/IISc Wistar rats following treatment of tumor bearing animals with M. tuberculosis H37Ra, pH 9.6 Image -asparaginase has been observed. Immunity in these rats was demonstrated by tumor rejection and detection of humoral antibodies in the sera to the antigen of the cell-free extract of the tumor. The enzyme was ineffective in inhibiting fibrosarcoma in mice at the dose levels tested.

Acylation of lysolecithin in the intestinal mucosa of rats

1. The presence of an active acyl-CoA–lysolecithin (1-acylglycerophosphorylcholine) acyltransferase was demonstrated in rat intestinal mucosa. 2. ATP and CoA were necessary for the incorporation of free [1-14C]oleic acid into lecithin (phosphatidylcholine). 3. The reaction was about 20 times as fast with [1-14C]oleoyl-CoA as with free oleic acid, CoA and ATP. 4. With 1-acylglycerophosphorylcholine as the acceptor, both oleic acid and palmitic acid were incorporated into the β-position of lecithin; the incorporation of palmitic acid was 60% of that of oleic acid. 5. Of the various analogues of lysolecithin tested as acyl acceptors from [1-14C]oleoyl CoA, a lysolecithin with a long-chain fatty acid at the 1-position was most efficient. 6. The enzyme was mostly present in the brush-border-free particulate fraction of the intestinal mucosa. 7. Of the various tissues of rats tested for the activity, intestinal mucosa was found to be the most active, with testes, liver, kidneys and spleen following it in decreasing order.

Biosynthesis of ubiquinone and ubichromenol in vitamin A-deficient rats

1. The concentrations of ubiquinone and ubichromenol increased in the livers, but not in the intestines and kidneys, of rats maintained on a diet deficient in vitamin 2. After short time intervals (e.g. 2 h) following administration of the tracer, incorporation of [2-14C]mevalonate into ubiquinone and ubichromenol in livers of vitamin A-deficient rats was lower than for normal animals; this was in contrast to later times (e.g. 72 h) when it was higher. 3. The “newly synthesized” ubiquinone in livers of vitamin A-deficient rats was distributed in all the cell fractions without specific localization. 4. Absorbed exogenous [14C]ubiquinone and [14C]ubichromenol were retained in the livers of vitamin A-deficient rats to a larger extent and for a longer time than in the normal animals. 5. The results suggest that the accumulation of ubiquinone and ubichromenol in the livers of vitamin A-deficient rats is due to lowered catabolism and not to increased rate of synthesis.

Effect of anti-luteinizing hormone serum on the ovulation of rats

IN the cyclic female albino rat, a release of pituitary luteinizing hormone (LH) occurs on the afternoon of proestrus1-5. This apparently induces ovulation, for ova are seen in the Fallopian tube 12 h later. Similarly, it is well known that in immature rats primed with pregnant mare serum gonadotrophin (PMS), ovulation can be induced by the administration of human chorionic gonadotrophin (HCG) or LH, the ova being seen in the Fallopian tube 12 h later. No information is available, however, about the mode of action of LH, released or administered, in bringing about ovulation. We have approached this problem by blocking the action of the ovulating hormone (LH) at various times after administration. © 1970 Nature Publishing Group.

Vitamin C status of vitamin A-deficient rats

IT was initially suggested that vitamin A-deficiency leads to an interference in the biosynthesis of ascorbic acid, because depletion of vitamin A was found to cause a fall in the tissue-levels of ascorbate and diminished urinary ascorbic acid excretion in animals1-3. Mapson4, however, concluded that lowered ascorbic acid-levels in vitamin A-deficient rats is due to inanition only, because he was able to show that following chloretone treatment vitamin A-deficient and pair-fed vitamin A normal rats excrete comparable amounts of ascorbic acid in their urine and that restriction of food intake reduces the urinary ascorbate even in the chloretone-treated normal rats. Results of our preliminary experiments reported here clearly indicate that the synthesis of ascorbic acid in rats is markedly reduced during vitamin A-deficiency.

Fatty acid specificity for the esterification of vitamin A and cholesterol by intestinal and pancreatic enzymes in rats

VITAMIN A and cholesterol esters have been shown to undergo extensive hydrolysis in the lumen of the small intestine during the process of absorption; they are re-esterified to appear in the lymph mostly as esters1,2. However, the vitamin A esters of the lymph, blood and liver of the rat are formed by long-chain fatty acids3 and in the normal rat liver, probably as palmitates4. On the other hand, cholesterol esters are usually made up of poly-unsaturated fatty acids in the lymph and blood of rats5. For the absorption of the two lipid materials, the enzymes of the pancreas have been largely implicated, while not much attention has been paid to the possible role of the mucosal enzymes. From the behaviour of the mucosal enzymes, as presented here, it appears that probably these enzymes play a more important part in the re-esterification of the two lipid materials during their absorption.

High cholesterol diet and esterification of cholesterol by the intestinal mucosa of rats

Young male rats maintained on a diet containing 1% cholesterol were sacrificed at the end of 1st, 2nd, 3rd, 5th, and 7th week. Acetone powders prepared from their intestinal mucosa and pancreas were tested for the synthetic and hydrolytic activities for Vitamin A and cholesterol esters. The esterifying activity of the mucosal enzymes for both Vitamin A and cholesterol increased progressively up to the end of the 5th week; the increase in esterification of cholesterol was more marked with respect to saturated fatty acids, as compared to the unsaturated ones. The pancreatic enzymes remained unaffected. It is suggested that one of the reasons for the accumulation of cholesterol esters in animal tissues may be the increased esterification of the sterol in the mucosa induced by dietary cholesterol.