Protective effects of Zizyphus oxyphyla on liver and kidney related serum biomarkers in (CCl4) intoxicate rabbits

The study was aimed to evaluate the therapeutic effects of Zizyphus oxyphyla leaves methanolic (ZOX-LME), on serum liver, kidney and hematology along with other serum parameters in Carbon tetrachloride (CCl4) intoxicated rabbits. Experimental animals were divided into five groups, six rabbits in each. These were: group NC (normal control), group, TC (toxic control) and group ST i.e. silymarine administered group at dose rate (50) mg/kg body weight (BW). Group ET1 and group ET2 treated with (ZOX-LME) at dose 200 mg/kg BW and 400 mg/kg BW. CCl4 administration caused significant (P> 0.05) impairment in serum liver enzymes, blood factors and other serum indices. Treatment with (ZOX-LME) significantly (P<0.05) reduced and normalized the levels of serum alanine transaminase (ALT) aspartate transaminase (AST) and alkaline phosphatase (ALP) and hematological indices. Also significant (P< 0.05) reduction was observed in creatinine, urea, uric acid, blood urea nitrogen (BUN), and albumin and glucose concentrations. The altered levels of lipid profile and serum electrolytes (Ca, Mg, Cl, Na, K, and P) were significantly (P<0.05) change toward normal levels with (ZOX-LME) feeding. In addition (ZOX-LME) ingestion caused significant improvement in GSH, GST and CAT levels, while reducing the TBARS levels, exhibited antioxidant capacity. Also (ZOX-LME) showed increase inhibition against percent scavenging of 2, 2-diphenile-1-picrylehydrazyle (DPPH) free radical. Significant (P<0.05) normalizing effects were observed with high dose 400 mg/kg BW of (ZOX-LME and were equivalent to silymarine administered groups. The histological study of liver supported the hepatoprotective and renal curative activity of (ZOX-LME).

Protective Effects of Chlorogenic Acid against Carbon Tetrachloride-Induced Hepatotoxicity in Mice

The protective effects of chlorogenic acid (CGA) against liver injury were evaluated by its reduction in carbon tetrachloride (CCl4)-induced hepatic damage in ICR mice. The animals were orally given CGA (60, 100, and 200 mg/kg, respectively) or silymairn (200 mg/kg) daily with 0.3% CCl4 administration (3 mL/kg, dissolved in olive oil) after medicament treatment on the 7th day. Compared with the normal group, CCl4 caused severe impairment in liver according to the evidence of significant reduction in the level of total albumin and expansion (p < 0.05) of the activities in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cholesterol, triglyceride (TG), and total albumin in serum, decreased the level of glutathione (GSH), and diminished the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and glutathione peroxidase (GSH-Px) in liver while increasing the level of hepatic thiobarbituric acid-reactive substances (TBARS). However, oral administration of CGA or silymarin could significantly (p < 0.05) decrease the serum levels of AST, ALT, cholesterol, TG, and total albumin and elevated the serum total albumin and the activities of GSH, catalase, SOD, GSH-Rd, and GSH-Px while leading to decline the TBARS in liver compared with CCl4-intoxicated group. Moreover, histopathology displayed that CGA decreased the formation of lesions in liver resulted from CCl4. The outcomes indicate that CGA shows the efficiency hepatoprotective consequences for CCl4-incited liver injuries in mice by the elevation of the activities of antioxidant enzymes and hindrance of lipid peroxidation.

Hepatoprotective Screening of Seriphidium kurramense (Qazilb.) Y.R. Ling

Investigation on medicinal plants’ therapeutic potential has gained substantial importance in the discovery of novel effective and safe therapeutic agents. The present study is aimed at investigating the hepatoprotective potential of Seriphidium kurramense methanolic extract (SKM) against carbon tetrachloride- (CCl4-) induced hepatotoxicity in rats. S. kurramense is one of the most imperative plants for its various pharmacological activities. Therefore, this study was aimed at evaluating the hepatoprotective potential against CCl4-induced liver toxicity. The serum samples were analyzed for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) together with the oxidative stress mediator levels as nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), reduced glutathione (GSH), and superoxide dismutase (SOD) as well as peroxidation and H2O2 activity. CCl4 administration resulted in an elevated free radical generation, altered liver marker (AST and ALT) enzymes, reduced antioxidant enzyme, and increased DNA damage. Methanolic extract of S. kurramense decreased CCl4-induced hepatotoxicity by increasing the antioxidant status and reducing H2O2 and nitrate content generation as well as reducing DNA damage. Additionally, SKM reversed the morphological alterations induced by CCl4 in the SKM-treated groups. These results demonstrated that SKM displayed hepatoprotective activity against CCl4-induced hepatic damage in experimental rats.

Evaluation of in vivo Hepatoprotective activity of Mimosa rubicaulis (LAM.) against CCL4 Induced Liver Toxicity

The current study was conducted to assess the hepatoprotective activity of different extracts of M. rubicaulis (Lam.) at (200 and 400 mg/kg) doses b.w. against CCl4 induced liver intoxication in Albino Wistar rats. Male or female Wistar rats about 150 and 200 gm body weight were selected for present study. The animals were divided into thirteen groups, six rats in each group. The extracts and Silymarin-treated animal groups significantly reduced the activities of various biochemical markers such as SGPT, SGOT, ALP, and TB which were elevated by carbon tetrachloride (CCl4) intoxication. The extracts of M. rubicaulis (Lam.) showed a dose dependent hepatoprotection activity. Among all the extracts, ethanolic extract produced maximum hepatoprotection (SGPT-83.15 %, SGOT76.82%, ALP-79.33%, TB-80.00%) at a 400mg/kg dose. After CCl4 administration, the levels of hepatic-antioxidant enzymes such as Glutathione (GSH) and Catalase (CAT) were reduced, whereas the level of hepatic lipid peroxidation (-LPO) increased. These hepatic antioxidant enzymes were also restored to normal levels by extracts and Silymarin treatment. The results of the present investigation indicate that all the extracts of M. rubicaulis (Lam.) possess hepatoprotective activity which may be due to the presence of various chemical constituents.

Therapeutic Effect of Dithiophenolato Chitosan Nanocomposites Against Carbon Tetrachloride-induced Hepatotoxicity in Rats

Our previous study showed that dithiophenolate (DTP) and its chitosan nanoparticles (DTP-CSNPs) have abilities to bind with DNA helixes. So in this study, their lethal doses (LD50) and therapeutic roles against rat liver injuries induced by carbon tetrachloride (CCl4) were evaluated. The study focused on the determination of the markers of oxidative stress (OS) and apoptosis and compare the results with those of cisplatin treatment. The results revealed that LD50 values of DTP and DTP-CSNPs are 2187.5 and 1462.5 mg/kg, respectively. Treatment with DPT and DPT-CSNPs after CCl4 administration reduced liver injuries, induced by CCl4, and improved liver functions and architecture through the reduction of OS and apoptosis. Where the oxidant marker was decreased with elevations of antioxidant markers. Also, there was an elevation in Bcl 2 value, with decreases in caspase-8, Bax, and Bax/Bcl 2 ratio. DPT-CSNPs treatment gave preferable results than that treated with DPT. Moreover, DTP and DPT-CSNPs treatment gave better results than Cisplatine treatment. The administration of healthy rats with low doses of DTP and DTP-CSNPs for 14 days had no effect. Otherwise, the study on HepG2 cell line showed that DTP and DPT-CSNPs inhibited cell growth by arresting cells in the G2/M phase and inducing cell death. In conclusion: DTP and DTP-CSNPs have anti-apoptotic and anti-oxidative stress towards hepatotoxicity induced by CCl4. Moreover, DTP and DTP-CSNPs have anticancer activity against the HepG2 cell line. Generally, DTP-CSNPs are more effective than DTP. So, they can be used in the pharmacological fields, especially DTP-CSNPS.

Quercetin Extracted from Broccoli Attenuates the Renewal of Hepatic Cells via Downregulation of TGFβ-1 and Arresting of HSCs Activation in Mice

Fibrosis of hepatic cells is a consequence of various etiologies of serious liver injury. Antifibrotic properties of quercetin extracted from broccoli were detected in mice with liver fibrosis induced by CCl4. These activities were assessed by investigating the liver enzymes ALT, AST, and Alb. Also, biochemical markers: TGFβ-1, HA, IL-6 level, and immunohistological markers PCNA and α –SMA analysis were observed and then compared and statically represented. A randomized controlled trial was applied on 21 mice that were grouped into 3 groups. The control group received water and standard feed. A positive control group took CCl4 (0.5μl/g) only. Therapeutic group took CCl4 (0.5μl/g) then quercetin (50mg/kg). Increases in ALT, AST, and biochemical markers (TGFβ-1, HA, IL-6) activities and decrease in Alb were observed in mice who received CCl4 only, in contrast to mice that took quercetin after CCl4 administration with statistically significant value p<0.001. After receiving quercetin, the immunohistological investigation assessed α –SMA downregulation, which certain ECM accumulation, but a renewal of fibrotic liver cells was detected with the raise of the regenerative marker PCNA within the liver cells. Quercetin extracted from broccoli may assist in the therapy and improving the recovery of the fibrotic liver.

Hepatoprotective activity of Cuscuta reflexa aqueous and alcoholic extracts against CCl4 induced toxicity in rats

Introduction In the present study the impact of aqueous and alcoholic extracts of Cuscuta reflexa were investigated on rats intoxicated with carbon tetrachloride (CCl4). CCl4 is known to intoxicate the liver of rats which can be easily be observed by examining the total protein, total bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine transaminase ALT). Cuscuta reflexa have been used in traditional medicine culture from time immemorial. In this study both the aqueous and alcoholic extracts of Cuscuta reflexa were found to have curative impact on liver profile of CCl4 intoxicated rats. Materials and Methods. The stem of Cuscuta reflexa were collected from host bougainvillea, dried in shade and were subjected to alcoholic (ethanolic), and aqueous extraction. Albino rats were intoxicated with CCl4 to induce hepatotoxicity. The CCl4 intoxicated rats were treated with low dose and high dose of both the extracts to assess the hepatoprotective impact on intoxicated rats. The results clearly revealed that the CCl4 administration altered liver profile. The altered liver profile parameters recovered to normal after administration of aqueous and alcoholic extracts. Results and Discussion. Administration of CCl4 induced hepatotoxicity in albino rats, which was evident with the results of serum analysis. Post CCl4 administration the liver profile parameters were altered. The CCl4 intoxicated rats were then treated with aqueous and alcoholic extracts of Cuscuta reflexa. Post treatment with the extracts the liver profile parameters recovered to normal. Conclusion: Present study reveals that aqueous and alcoholic extracts of Cuscuta reflexa were found to have curative impact on liver profile of CCl4 intoxicated rats. Keywords: Custuca reflexa, CCl4, hepatoprotective, liver profile, alcoholic extract, aqueous extract,

Immunopathological mechanisms of toxic damage to the liver, thymus and spleen

Objective: to establish the features of the immune response in the early stages of diffuse toxic damage. Materials and methods. Diffuse toxic liver damage of male Wistar rats was caused by a single intraperitoneal injection of an oil solution of carbon tetrachloride (CCl4) at a dose of 50 mg/100 g. Animals were carried out from the experiment on days 3, 7 and 14. The study included hematological and histological analysis, immunohistochemical (IHC) staining of liver, thymus and spleen tissues, quantitative evaluation of CD3+, CD45RA+ (T-and B-lymphocytes), F4/80+ (macrophages), and HSP70+-cells. Results. CCl4 administration has been shown to cause structural disorders of liver, thymus, and spleen tissue. In the early stages, there is an increase in CD3+-cells in the liver and spleen, while CD45RA+-cells predominating in the thymus. On the 3rd day after CCl4 administration, the number of F4/80+-cells in the liver increases by 56.7%, in the thymus and spleen by 21% and 19.3%, respectively, there is also an increase in the number of HSP70+-cells roughly 2 times in the liver and thymus, and by 7 times in the spleen. Conclusion. Hepatotropic poison CCl4 causes damage not only the liver but the organs of immunopoesis. In the early stages of exposure to the toxicant the predominant population is T-lymphocytes (CD3+-cells) in the liver and spleen, and B – lymphocytes (CD45RA+-cells) in the thymus. In all the studied organs, the number of macrophages increases on the 3rd day of the experiment, and significantly decreases at the later term. This fact indicates that macrophages act as a target of toxic effects. The increase in the number of HSP70+-cells in the liver, thymus, and spleen in response to toxic damage is likely aimed at triggering the repair or elimination of denatured proteins that are toxic to the cell.

Malondialdehyde (MDA) as a Marker of Platelet Function in Rats with CCl4-Induced Toxic Hepatopathy

Blood platelets are pivotal cells in the process of hemostasis and thrombosis. In the majority of patients with severe liver disease, platelet function appeared defective. We determinate platelet adhesiveness, aggregability and MDA level, in rats with acute and chronic hepatopathy induced by CCl4 administration. Our data relieves that platelet functions are not only affected in chronic toxic affectation, but also in acute intoxication (p[0.05). Icosanoids production (expressed in MDA levels) are significantly decreased only in chronic CCl4 intoxication (p[0.001). Significant correlation appears between aggregability and MDA (r = -0.78) and adhesiveness and MDA (r = -0.57) in group C, with chronic CCl4 intoxication. The complexity of these platelet functions related to the hepatic disease is still a matter of debate and needs further investigation.

Increased Purinergic Responses Dependent on P2Y2 Receptors in Hepatocytes from CCl4-Treated Fibrotic Mice

Inflammatory and wound healing responses take place during liver damage, primarily in the parenchymal tissue. It is known that cellular injury elicits an activation of the purinergic signaling, mainly by the P2X7 receptor; however, the role of P2Y receptors in the onset of liver pathology such as fibrosis has not been explored. Hence, we used mice treated with the hepatotoxin CCl4 to implement a reversible model of liver fibrosis to evaluate the expression and function of the P2Y2 receptor (P2Y2R). Fibrotic livers showed an enhanced expression of P2Y2R that eliminated its zonal distribution. Hepatocytes from CCl4-treated mice showed an exacerbated ERK-phosphorylated response to the P2Y2R-specific agonist, UTP. Cell proliferation was also enhanced in the fibrotic livers. Hepatic transcriptional analysis by microarrays, upon CCl4 administration, showed that P2Y2 activation regulated diverse pathways, revealing complex action mechanisms. In conclusion, our data indicate that P2Y2R activation is involved in the onset of the fibrotic damage associated with the reversible phase of the hepatic damage promoted by CCl4.