Swertiamarin attenuates carbon tetrachloride (CCl4)-induced liver injury and inflammation in rats by regulating the TLR4 signaling pathway

The aim of the present study is to illustrate the effects of swertiamarin (STM), a natural iridoid from herbal medicines, on hepatic inflammation induced by carbon tetrachloride (CCl4) in rats. Male Sprague Dawley rats were exposed to CCl4 with or without STM co-administration for 8 weeks. Our results revealed that STM administration (100 and 200 mg/kg b.w.) significantly attenuated inflammation in livers of CCl4-treated rats. STM remarkably reduced the production of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-1a (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) in liver tissue of CCl4-treated rats. In addition, STM treatment downregulated connective tissue growth factor (CTGF) and ser307pIRS-1 expression, which was induced by CCl4 exposure. In the process of exploring the anti-inflammatory mechanisms of STM action, we demonstrated that STM significantly inhibited Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) p65 expression in the liver. In conclusion, these results suggested that the inhibition of CCl4-induced inflammation by STM was, at least in part, due to its regulation of the TLR4 /NF-κB signaling pathway

Hepatoprotective effect of some drugs in experimental model of acute liver injury

Acute liver injury is a clinical condition that results from severe extensive damage of liver tissue associated with Jaundice and it is experimentally induced by hepatotoxic agents like ccl[4]. Thirty five healthy rabbits were involved in the present study. They were allocated to five groups. Each group was given one of the following agents: vitamin E, zinc sulfate, amlodipine besylate, distilled water two hours before administration of ccl[4]. The same doses of the tested agents were continued for two days after ccl[4] administration. The effect of drugs was evaluated at two occasions 24 and 72 hours after ALI induction on the basis of biochemical analysis of liver function tests as well as histopathological examination to the liver of treated animals. All the tested agents produced significant reduction in ALT, AST, ALP, and TSB with a significant elevation of TSP levels as compared with treated control group. The histopathological examination showed clear improvements in the sections of liver tissue that support the effect of these agents on the liver. The study showed that 30% of women were anemic; the effect of anemia on thyroid function was not clear as 98% of the studied women have normal thyroxin and only 1% has low thyroxin level while 1% showed high concentration of thyroxin level. All the tested agents proved to have hepatoprotective effect of varying degree on ALI model

Antioxidant activities of the leaves Chrysophyllum albidum G.

Chrysophyllum albidum G. is a tropical plant and commonly found in Nigeria. It belongs to the sapotaceae family and used in folklore in the treatment of yellow fever, malaria, diarrhea, vaginal and dermatological infections. The study was aimed at investigating the antioxidant properties of this plant by employing the in vitro and in vivo experimental models. The effect of DPPH free radical scavenging activity on the fractions of petroleum ether, ethanol, butanol, ethylacetate, and water of C. albidum was determined. The ethyl acetate fraction was purified in column chromatography to obtain myricetin rhamnoside. Structure elucidation was done by NMR and mass spectroscopic techniques. Furthermore, ethanol extract was administered to five groups of eight rats per group. The animals in the normal group were administered with vehicle alone for 7 days. The positive control animals were given vehicle on the first four days, and with the vehicle and hepatotoxin [CC1[4]] on the fifth, sixth and seventh day. The animals in the treatment category were respectively administered with 500, 1000 and 1500 mg/kg b.w. of extract and distilled water for the first four days, and with distilled water, extract and CC1[4] on the last three days. Animals were subsequently anaesthetized and blood samples were collected for catalase [CAT], malondialdehyde [MDA], reduced gluthathione [GSH] and superoxide dismutase [SOD] assays. The petroleum ether fraction showed the least antiradical activity [4057.5 +/- 809.6 g/kg] while ethyl ether exhibited the highest activity [414.4 +/- 92.0 g/kg]. Myricetin rhamnoside also exhibited an excellent radical scavenging activity [314.1 +/- 60.2] which was comparable to the positive control. Result from animal study showed that C. albidum exhibited significant [p < 0.05] differences on the activity of CAT, MDA and GSH. The plant could therefore be employed as sources of natural antioxidant boosters and for the treatment of some oxidative stress disorders in which free radicals are implicated

Reversal of hepatotoxin-induced pre-fibrogenic events by Emblica officinalis--a histological study.

Efficacy of a herbal product of E. officinalis (fruit) (EO) has been evaluated against carbon tetrachloride (CCl4) and thioacetamide (TAA) induced changes in rat liver. Chronic treatment of CCl4 and TAA revealed abnormal histopathology indicative of pre-fibrogenic events. EO reversed such alterations with significant regenerative changes suggestive of its preventive role in prefibrogenesis of liver.

Larval susceptibility of Ajuga remota against anopheline and culicine mosquitos.

The objective of the present study is to determine the bioefficacy of different crude extracts of Ajuga remota against anopheline and culicine larvae. Larval susceptibility of crude carbon-tetrachloride, methanol and petroleum-ether extracts of Ajuga remota leaves was observed against the malaria vector, Anopheles stephensi and the filariasis vector, Culex quinquefasciatus. Among the extracts tested, petroleum-ether extract was the most effective with LC50 values of 0.033% after 24 hours and 0.029% after 48 hours of treatment against the larvae of Anopheles stephensi. In the case of the larvae of Culex quinquefasciatus, the carbon-tetra-chloride extract exhibited maximum efficacy with LC50 values of 0.043% after 24 hours and 0.026% after 48 hours of exposure, respectively. It is, therefore, concluded that Ajuga remota can be applied as an ideal larvicide against An. stephensi and Cx. quinquefasciatus.

Fructose, 1,6-diphosphate mitigates CCl4 suppressed nitric oxide synthase activity in rats.

Effect of fructose 1,6-diphosphate (FDP) and carbon tetrachloride (CCl4) were studied individually and in combination on rat endothelial (ET) and smooth muscle cell (SMC) nitric oxide synthase (NOS) activities in vivo, inhibition of ET and SMC NOS activity in CCl4 treated rats was reversed in FDP + CCl4 treated animals. Cellular based NOS activity was significantly increased in FDP treated group of rats when compared to non treated controls. The results suggest a significant increase in NOS in rats treated with a combination of FDP + CCl4 thus overcoming the suppression of NOS exposed to CCl4 alone.

Effect of fumigation and juvenile hormone on oxygen consumption of the larvae of Corcyra cephalonica (Stainton).

Reduced effect of JH-I, JH-II and JH-III on oxygen consumption of II-V instars and increased effect on the oxygen consumption of VI instar larvae suggested that control of corcyra with juvenile hormones could be brought about only when applied to just emerged VI instar larvae. Similarly fumigation of juvenile hormone treated larvae could prove beneficial only at VI instar stage. The possibility of enhancing the effect of fumigant with pretreatment of JH will be futile as even only JH treated VI instar larvae develop into abnormal individuals which die later.

Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride

The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.

Induction of tumour necrosis factor alpha in experimental animals treated with hepatotoxicants.

Administrations of hepatotoxicants namely carbon tetrachloride (CCl4:0.4 ml in 1.2 ml of liquid paraffin) and ANIT (1 ml of 1.5% solution in liquid paraffin) in Charles foster rats (force fed) and D-galactosamine (8 mg in water per swiss albino mouse, ip) induce the release of TNF-alpha in case of CCl4 and D-galactosamine. High TNF-alpha level was observed up to 48 hr in CCl4 and up to 24 hr in D-galactosamine treated animals. Elevated levels of biochemical like ALP and SGPT are also recorded. TNF-alpha level can be measured of tissue damage and prognosis in case of hepatitis.

Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride.

Andrographolide, a diterpenoid lactone, was isolated (yield 0.78% w/w) from A. paniculata (whole plant). Its LD50 in male mice was 11.46 g/kg, ip. Antihepatotoxic activity of andrographolide (100 mg/kg, ip) was compared with 861.33 mg/kg, ip, of the methanolic extract (equivalent to 100 mg/kg of andrographolide) and 761.33 mg/kg ip, of the andrographolide-free methanolic extract (equivalent to 861.33 mg/kg of the methanolic extract) of the plant, using CCl4-intoxicated rats. Biochemical parameters like serum transaminases--GOT and GPT, serum alkaline phosphatase, serum bilirubin and hepatic triglycerides were estimated to assess the liver function. Overall inhibition of CCl4-induced increase in the five biochemical parameters was found to be 48.6 per cent (andrographolide), 32.0 per cent (methanolic extract) and 15.0 per cent (andrographolide-free methanolic extract). These biochemical observations were supplemented by histopathological examination of the liver slices. Further, andrographolide (100 mg/kg, ip) was found to normalize completely the CCl4-induced increase in the pentobarbitone induced sleep time of mice. The results suggest that andrographolide is the major active antihepatotoxic principle present in A. paniculata.