CCl4-induced Toxicity Research Articles

Exploring the antioxidant and protective effects of Marsdenia thyrsiflora Hook.f. leaf extract against carbon tetrachloride-induced hepatic damage in rat models.

Medicinal plants are vital to healthcare, yet many remain unexplored. Marsdenia thyrsiflora Hook.f., from Bangladesh's Bhawal Forest, lacks research on its medicinal properties, especially its antioxidant capacities and protection against CCl4-induced liver toxicity. This study aims to evaluate the antioxidant properties of M. thyrsiflora leaf extract to determine its protective effects on rodents against CCl4-induced liver injury. After extraction, the total phenol, flavonoid content, and antioxidant capacity of the leaf extract were measured using established protocols. Free radical scavenging abilities were evaluated with 2,2'-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) assays. Additionally, reducing power was assessed through cupric-reducing and ferric-reducing assays. Based on the OECD 420 recommendation, acute toxicity was tested on Swiss albino mice to establish an effective and safe dosage. For the hepatoprotective study, Sprague-Dawley rats were pre-treated with M. thyrsiflora leaf methanolic extract (MTLM) at 250 and 500mg/kg body weight, and CCl4 was administered to induce liver damage. Serum hepatic enzyme levels (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT)), lipid profile (total cholesterol, triglycerides), total bilirubin, and markers of lipid peroxidation (Malondialdehyde (MDA)) were measured. The activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were also evaluated to assess oxidative stress. The results demonstrated that MTLM, rich in phenolic and flavonoid content, exhibits significant antioxidant activities in DPPH and NO radical scavenging assays, as well as in reducing power assays. The acute toxicity study confirmed the safety of MTLM, with no adverse effects observed even at high doses. For the hepatoprotective study, rats were administered CCl4 to induce liver damage, followed by treatment with MTLM. Results showed that MTLM significantly reduces liver damage markers such as elevated serum hepatic enzyme levels, lipid profile, total bilirubin, and lipid peroxidation and improves the activities of GSH and key antioxidant enzymes such as SOD and CAT. Histopathological analysis corroborated these findings, displaying reduced necrosis, inflammation, and edema in liver tissues treated with MTLM. MTLM extract exhibits potent antioxidant and hepatoprotective properties. Its ability to attenuate oxidative stress, enhance antioxidant enzyme activities, and facilitate histopathological changes in the liver highlights its potential as a natural therapeutic agent for liver damage. However, further investigation is required to understand its molecular processes, safety profiles, and active component characterization.

Effect of CCl4 on Renal Tissues of Male Mice and Prevented by Pretreatment with Bromelain Loaded with Gold Nanoparticles: Histopathological and Caspase-9 Expression Alterations

The study aimed to investigate the potential protective effect of bromelain on renal histopathological changes induced by carbon tetrachloride (CCl4) in albino mice. CCl4 is widely used in the chemical industry but is also known to cause toxicity to various organs including the brain, liver, kidneys and lungs. In this study, 49 animals were divided into 7 equal groups. The kidneys of the mice were examined to assess histopathological changes and immunohistochemical markers, specifically caspase-9. The groups that received bromelain solution coated with gold nanoparticles demonstrated greater protective effects against CCl4-induced kidney damage. The findings suggest that kidney damage induced by CCl4 may be attributed to oxidative stress, which disrupts the antioxidant defense system, enzyme function and biochemical markers. However, administration of bromelain significantly mitigated CCl4 toxicity by enhancing the antioxidant defense system and reducing the production of free radicals. Notably, the study found that a dose of 300 mg of bromelain effectively reduced CCl4-induced toxicity in rats. This highlights the potential therapeutic value of bromelain in protecting against chemical-induced kidney damage. HIGHLIGHTS The kidney damage from carbon tetrachloride can occur through oxidative stress, altering the antioxidant defense system, enzyme function, and biochemical markers. The bromelain can decreased the toxicity of CCL4. The 300 mg bromelain solution proved to be more efficacious than the 100 mg dose. GRAPHICAL ABSTRACT

Potential of CME@ZIF-8 MOF Nanoformulation: Smart Delivery of Silymarin for Enhanced Performance and Mechanism in Albino Rats.

Silymarin, an antioxidant, is locally used for kidney and heart ailments. However, its limited water solubility and less oral bioavailability limit its therapeutic efficiency. The present study investigated the enhancement of solubility and bioavailability of silymarin by loading it in Cordia myxa plant extract-coated zeolitic imidazole framework (CME@ZIF-8) against carbon tetrachloride (CCl4)-induced nephrotoxicity and cardiac toxicity in albino rats. The synthesized PEG-coated silymarin drug-loaded CME@ZIF-8 MOFs (PEG-Sily@CME@ZIF-8) were characterized by scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and zeta potential. The average crystal size of CME@ZIF-8 and PEG-Sily@CME@ZIF-8 was 12.69 and 16.81 nm, respectively. The silymarin drug loading percentage in PEG-Sily@CME@ZIF-8 was 33.05% (w/w). In the animal model with CCl4 treatment, different parameters like serum profile, enzymatic level, genotoxicity, and histopathology were assessed. Treatment with PEG-Sily@CME@ZIF-8 with different doses of 500, 1000, and 1500 μg/kg body weight efficiently ameliorated the alterations in the antioxidant defenses, biochemical parameters, and histopathological alterations and DNA damage in comparison to silymarin drug in a CCl4-induced toxicity rat model via alleviating the cellular abnormalities and attenuation of normal antioxidant enzymes levels. Moreover, the molecular mechanism of drug-silymarin interaction with the target protein was investigated. It involves the binding pockets of silymarin molecules with VEGFR, TNF-α, NLRP3, AT1R, NOX1, RIPK1, Caspase-3, CHOP, and MMP-9 proteins, elucidating the silymarin-protein interactions by the formation of hydrogen bonds and hydrophobic interactions. This study suggests that the nanodrug PEG-Sily@CME@ZIF-8 MOFs protect the kidneys and heart possibly by mitigating oxidative stress more efficiently than the conventional drug silymarin.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

Fabrication of a decellularized liver matrix-based hepatic patch for the repair of CCl4-induced liver injury.

This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin-DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin-complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.

A comparative study on the protective effects of cuminaldehyde, thymoquinone, and gallic acid against carbon tetrachloride-induced pulmonary and renal toxicity in rats by affecting ROS and NF-κB signaling

CCl4 toxicity is a fatal condition that can cause numerous organ dysfunctions. We evaluated and compared the protective effects of cuminaldehyde (CuA), thymoquinone (TQ), and gallic acid (GA) on CCl4-induced pulmonary and renal toxicity in rats. The impacts of these compounds on CCl4-induced oxidative stress, inflammation, and morphological alterations were examined. The results showed that the compounds under investigation prevented CCl4 from significantly increasing pulmonary and renal lipid peroxidation and NO levels, as well as massively depleting GSH levels and GPX and SOD activities. Moreover, they suppressed the CCl4-induced increase in mucus secretion in the lung and upregulated the gene expression of pulmonary and renal NF-ҡB, iNOS, TNF-α, and COX-2. The heatmap cluster plots showed that GA and TQ had better protective potencies than CuA. The external organ morphology, histopathological results, and chest X-ray analysis confirmed the toxicity of CCl4 and the protective influences of the tested compounds in both the lungs and kidneys of rats. These compounds displayed predicted competitive inhibitory effects on iNOS activity and may block the IL-13α2 receptor, as revealed by molecular docking analysis. Thus, CuA, TQ, and GA, particularly the latter two, are prospective protective compounds against the pulmonary and renal toxicity caused by CCl4.

Quercetin and hesperidin protection against hepato-renal damage occasioned by carbon tetrachloride (CCL4) in a rat model

BackgroundCurrent pharmacological research has shown that medicinal plants have notable bioactivities. For more than a millennium, traditional Chinese medicine (TCM) has prescribed CRP primarily as a qi-regulating medication for therapeutic purposes. Hence, the synergistic effect of the two medicinal plants on the hepato-renal damage in rats exposed to CCL4. Materials and MethodsFor twenty-one days, rats were gavaged with quercetin and hesperidin (2.4 and 2.4 mg/kg each) after being exposed to CCL4 (0.5 mg/kg). Samples were taken to evaluate several biochemical markers. Nitric oxide (NO), hydrogen peroxide (H2O2), and malondialdehyde (MDA) were measured. The activity of the enzymes alanine transferase (ALT) and alkaline phosphatase (ALP) were estimated to represent liver function. Catalase (CAT), Glutathione peroxidase (GPx), and Glutathione (GSH) levels were evaluated for antioxidant level, total bilirubin, total protein, urea, uric acid, and creatinine), as well as histopathology were assessed. ResultsThe concentration of total bilirubin, total protein, urea, uric acid, creatinine, increased considerably (P < 0.05) after exposure to carbon tetrachloride, with the levels of H2O2, MDA, SOD, CAT, GPX, GSH, and the activities of ALT and AST in serum, also, changes observed in histopathological findings. Upon treatment with the extracts, the levels of H2O2 and MDA was significantly (P < 0.05) reduced and modify SOD, CAT, GPX, GSH, ALT, and ALP activities in rats substantially (P < 0.05). With slid changes on histopathological effect. ConclusionQuercetin and hesperidin treatment successfully improved liver and kidney pathophysiology and reduce the level of ROS. Thus, quercetin and hesperidin can be recommended as a hepato-renal preventive agent against CCL4-induced toxicity.

Assessment of hepatoprotective and nephroprotective effects of Vitis vinifera leaf extract on carbon tetrachloride induced toxicity in rats

Background: Vitis vinifera is known for its antimicrobial activity; however, the hepatoprotective activity of aqueous extracts of aerial parts has also been reported, but the nephroprotective and hepatoprotective activity of ethanolic extracts have not yet been evaluated. Objective: To evaluate Vitis vinifera's hepatoprotective and nephroprotective activities against CCl4-induced toxicity in rats. Methods: Two doses of ethanolic extract of Vitis vinifera (100 and 200 mg/kg/day) were evaluated and compared with silymarin 100 mg/kg. Biochemical blood parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Gamma-glutamyltranspeptidase (GGT), bilirubin, urea, uric acid, total protein and creatinine, and histopathologic changes of liver and kidney were studied and evaluated. Results: Vitis vinifera reduced the elevated blood levels of ALT, AST, ALP, urea, and creatinine, with the ethanol extract to 200 mg/kg/day being more effective. The histopathologic evaluation suggested that Vitis vinifera decreased hepatic and renal necrosis induced by CCl4. The more significant dose resulted in reductions in AST, ALT, GGT, ALP, and bilirubin of 54, 27, 56, 36, and 17%, respectively. Ethanolic extract 200 mg/kg/day also shows a reduction in elevated levels of Creatinine, Urea, Uric Acid, and Total Protein by 61%, 58%, 29%, and 9%, respectively. Conclusion: Hepatoprotective and nephroprotective activities of ethanol extract of Vitis vinifera were demonstrated, with ethanol extract to 200 mg/kg/day being the most effective. This presents scientific evidence for using medicinal plants such as Vitis vinifera in managing liver and kidney disorders.

Evaluation of the Potential Protective Role of Galangin Associated with Gold Nanoparticles in the Histological and Functional Structure of Testes of Adult Male Albino Mice Administrated with Carbon Tetrachloride

Galangin (Gal) is a natural flavonoid sourced from the roots of the plant Albina Kalanga. It possesses a variety of pharmacological activities, such as antioxidant, anticancer, and anti-inflammatory. The current study aims to enhance the efficacy of galangin through the use of gold nanoparticles as a drug delivery system against CCl4-induced toxicity in the testicular tissue of male albino mice. Forty-two albino mice were divided into seven groups (6 mice/group), treatment with carbon tetrachloride solution for two weeks by intraperitoneal injection, (1 ml/kg) once a week for all groups except the control group, after which a group was injected with gold nanoparticles and two groups were injected with galangin in two concentrations, and two groups were injected with AuNPs + Gal conjugation solution with two concentrations. The animals' bodies were weighed and blood samples were obtained for testosterone hormone analysis and testicles for the purpose of weighing and histological study at the end of the experiments. The study showed that the testicular tissue of mice treated with CCl4 had a different pathology compared to the control group, the testosterone hormone levels in the CCl4 group were significantly higher than those of the control group. Results from the AuNPs+Gal group showed a significant reduction in the effects of CCl4 toxicity on mice testicles, with testosterone levels are returning to normal and histological testicle structures improving, the ratio of testicle weights to animal body weight in the group injected with AuNPs was significantly higher than that of the control and CCl4 groups. In conclusion, the results revealed that galangin combined with gold nanoparticles could effectively reduced the histological and functional tissue damages caused by CCl4, presenting a promising natural solution that needs to be further developed

Carbon Tetrachloride-Induced Testicular Toxicity and Histopathological Alteration in Male Swiss Albino Mice

Recently there has been an increased association between toxic substances present in the environment and male infertility. Carbon tetrachloride (CCL4) is widely used as a chemical intermediate and as a feedstock in the production of chlorofluorocarbons. CCL4 is highly toxic to the liver, kidney, testicle, brain and other tissues. Therefore, the present study was designed to identify its effect on the reproductive system in adult male mice. Thirty adult male albino mice were divided into three equal groups (n=10): the first group control, the second group received 0.1m/100g body weight olive oil and the third group received 0.1ml/100g/body weight CCL4 intraperitoneally every alternate day for three weeks. The results showed that CCl4 causes a significant decrease in body weight, sperm motility, sperm count and testosterone level, while it leads to a significant increase in the number of abnormal sperm morphology. Additionally, CCL4 caused apparent alterations in the histological structure of the testes. In conclusion, CCl4-induced reproductive toxicity in male mice.

Evening primrose oil enriched with gamma linolenic acid and D/L-alpha tocopherol acetate attenuated carbon tetrachloride-induced hepatic injury model in male rats via TNF-α, IL-1β, and IL-6 pathway

The modulatory role of primrose oil (PO) supplementation enriched with γ-linolenic acid and D/L-alpha tocopherol acetate against a carbon tetrachloride (CCl4)-induced liver damage model was assessed in this study. Twenty male Albino rats were divided into four groups. The control group received corn oil orally. The PO group received 10 mg/kg P O orally. The CCl4 group received 2 mL/kg CCl4 orally and PO/CCl4 group; received PO and 2 mL/kg CCl4 orally. The relative liver weight was recorded. Serum liver enzymes, hepatic malondialdehyde (MDA), hepatic reduced glutathione (GSH) and the expression of hepatic tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were assessed. The binding affinities of γ-linolenic acid and D/L-alpha tocopherol constituents with IL-1β, IL-6 and TNF-α were investigated using molecular docking simulations. Histopathological and electron microscopic examinations of the liver were performed. The results indicated that CCl4 elevated serum liver enzyme and hepatic MDA levels, whereas GSH levels were diminished. The upregulation of IL-1β, IL-6, and TNF-α gene expressions were induced by CCl4 treatment. The PO/CCl4-treated group showed amelioration of hepatic injury biomarkers and oxidative stress. Restoration of histopathological and ultrastructural alterations while downregulations the gene expressions of TNF-α, IL1-β and IL-6 were observed. In conclusion, evening primrose oil enriched with γ-linolenic acid and D/L-alpha tocopherol acetate elicited a potential amelioration of CCl4-induced hepatic toxicity.

The Inhibitory Effect of Geraniol on CCL4-induced Hepatorenal Toxicity in Pregnant Mice through the PI3K/AKT Signaling Pathway.

Hepatotoxicity caused by CCL4 is well known. Geraniol (GNL) has high antioxidant effect that can induces liver regeneration. However, the protective effect of GNL effect on CCL4-induced hepatorenal toxicity in pregnant mice has not yet been studied. To investigate whether GNL could protect against oxidative stress induced by CCL4 via the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which is regulated by phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and has been found to have protective effects on renal and hepatic tissues. Forty-eight female albino mice weighing 25-30 g were randomly allocated to 4 groups: Group I served as a control; Group II received a toxicity-inducing single dose of 15 μL of CCL4 on the 4th day after mating; Group III received 40 mg/kg GNL + CCL4 (with GNL from the 1st day of assimilation to delivery); and Group IV received GNL alone from the 1st day of assimilation to the end of the delivery period. GNL was evaluated for its protective effects on hepatotoxicity in CCL4-treated pregnant mice. Litter size, weight, survival rate, and resorption were recorded. In addition, H & E staining was done for liver and kidney pathology as well as biochemical markers and oxidative markers malondialdehyde, superoxide dismutase, and catalase were analyzed. CCL4 significantly reduced survival rate and increased resorption after exposure. Alanine transaminase and aspartate aminotransferase concentrations in the serum, tissue MDA, blood urea nitrogen, and creatinine were increased after CCL4 exposure. GNL improved enzyme and antioxidant levels and prevented CCL4-induced hepatic injury in mice. Caspase-3 cleavage was decreased by GNL, which increased PI3K, phosphorylated AKT, Nrf2, and B-cell lymphoma 2. GNL demonstrates a protective effect against CCl4-induced hepatorenal toxicity, mediated through the activation of the PI3K/AKT signaling pathway and the upregulation of Nrf2. These findings highlight the potential therapeutic implications of GNL in mitigating oxidative stress and inflammation in liver and kidney tissues.

Hepatoprotective efficacy of Lagenaria siceraria seeds oil against experimentally carbon tetrachloride-induced toxicity.

The liver is crucial for maintaining normal metabolism in the body. Various substances, such as toxic chemicals, drugs, and alcohol, can damage hepatocyte cells, leading to metabolic imbalances. The experiment aimed to determine the efficacy of Lagenaria siceraria seed oil (LSS) as a hepatoprotective agent against acute hepatotoxicity triggered by carbon tetrachloride (CCl4). A total of 20 rats were randomly separated into four groups. The control group: rats received 2 ml of distilled water orally, followed by 1.25 ml of olive oil intraperitoneally (i.p.) after 30 minutes. CCL4 group: rats were given a single intraperitoneal dose of 1.25 ml/kg b.w. of CCl4 in a 1:1 mixture with olive oil. Silymarin group: received 100 mg of silymarin per kg of b.w. diluted in 2 ml of distilled water orally, followed by CCl4 treatment after 30 minutes. LSS oil group: received LSS oil at 3g/kg b.w. orally, followed by CCl4 treatment after 30 minutes. Blood samples were collected to assess liver enzymes (AST, ALT, and ALP), proteins and bilirubin fractions, and redox status (catalase, reduced glutathione (GSH), and malondialdehyde (MDA)) were assessed in hepatic tissues. Changes in liver histopathological examination were also evaluated. In CCl4-treated rats, there was a significant increase in serum liver marker enzyme activity (ALP, AST, and ALT) along with a significant elevation (p < 0.05) in total bilirubin, indirect bilirubin, and direct bilirubin compared to the control rats. However, all these parameters decreased in the CCl4+ Silymarin and CCl4+LSS groups compared to CCl4-treated rats. There was a significant decline in total protein level and serum albumin in all experimental groups compared to the control, while globulin levels significantly increased in all experimental groups. There was a significant (p < 0.05) reduction in the level of GSH and catalase, with an increase in MDA level in CCl4 rats compared to other rats. Histopathological investigation of the LSS-treated group showed a hepatoprotective effect against CCl4. The study revealed that LSS oil has antioxidant activity against CCl4-induced toxicity.

Mangiferin Ameliorates CCl4-Triggered Acute Liver Injury by Inhibiting Inflammatory Response and Oxidative Stress: Involving the Nrf2-ARE Pathway.

Acute liver injury (ALI) is characterized by inflammation and oxidative stress (OS). Although mangiferin (MGF) has antioxidant and anti-inflammatory effects, its role in ALI remains unclear. Accordingly, we investigated the MGF molecular mechanism in carbon tetrachloride (CCl4)-induced ALI in vivo and in vitro. The CCl4 was utilized to induce ALI in mice. In vivo, the therapeutic effects of MGF on CCl4-induced liver injury were evaluated through biochemical assays and histomorphological analysis. Additionally, immunohistochemistry, immunofluorescence, ELISA and Western blotting were further applied to explore the mechanism. In vitro, The CCK-8 assay and flow cytometry were employed to investigate the protective effects of MGF against CCl4-induced toxicity in HepG2 cells, while mitochondrial reactive oxygen species levels and Western blotting were used to explore the biological effects and molecular mechanisms. MGF treatment resulted in a reduction in serum levels of AST and ALT, diminished concentrations of TNF-α, IL-6, and IL-1β in liver tissue, and concurrently decreased cellular apoptosis. Furthermore, MGF pretreatment enhanced the activity of SOD and GSH while concurrently diminishing the MDA production. This study further demonstrated the upregulation of Nrf2, NQO1, and HO-1 protein expression levels, as well as the downregulation of p-p65 protein expression levels. In vitro investigations revealed that the mitigation of CCl4-induced inflammation and OS by MGF was mediated via the Nrf2- antioxidant response element (ARE) pathway, which was disrupted by ML385 in HepG2 cells. CCl4 can induce liver injury, while treatment with MGF mitigates ALI by inhibiting oxidative stress, inflammation, and apoptosis. The protective mechanism of MGF is mediated by the Nrf2-ARE pathway activation.

The Nephroprotective Potential of Brassica nigra Sprout Hydroalcoholic Extract against Carbon Tetrachloride-Induced Renal Toxicity in Rats.

The nephroprotective potential of the Brassica nigra sprout (BNS) hydroalcoholic extract against carbon tetrachloride (CCl4)-induced renal toxicity in rats was the object of this study. B. nigra sprouts were prepared in the lab to monitor the bio-changes in bioactive compounds during the sprouting for up to 7 days at 17 ± 1 °C and 90% relative humidity. Subsequently, 6-day sprouts of B. nigra were selected according to their phenolics and antioxidant activity, extracted, and examined for their nephroprotective and antioxidative stress potential at 250 and 500 mg sprout extracts kg-1 bw, in vivo. Weight gain, organ weight, lipid profile, atherogenic index, kidney functions, and oxidative stress biomarkers were assessed. The results indicated that the most proficient treatment for weight gain improvement was BNS extract at 500 mg kg-1. BNS at 250 mg kg-1 was remarked as the lowest weight gain enhancer compared to the NR group. A significant increase in TG, TC, LDL-c, and VLDL-c levels in the rats with CCl4-induced renal toxicity, and a significant decrease in HDL level, was noted. The administration of the BNS extract at 250 and 500 mg kg-1 considerably attenuated TG, TC, LDL-c, and VLDL-c levels, compared to the NR group. The most efficient treatment for improving the lipid profile was the BNS extract at 500 mg kg-1, even better than 250 mg kg-1. Administrating the BNS extract substantially attenuated the alterations in the creatinine, urea, and BUN caused by the CCl4 injection. The most efficient improvement was markedly recorded with the BNS extract at 500 mg kg-1, compared to the NR group. The rats treated with the BNS extract showed significant enhancement in GSH, CAT, and SOD activities and a considerable reduction in MDA levels. Administering the BNS extract at 250 and 500 mg kg-1 can efficiently reverse CCl4 inhibition of antioxidant enzyme activities, significantly increase GSH, CAT, and SOD, and decrease the MDA levels dose-dependently. The BNS extract at 250 and 500 mg kg-1 exhibits nephroprotection and antioxidative stress in a dose-dependent matter. The total nephroprotection % was recorded at 65.18% and 99.21% for rats treated with 250 and 500 mg kg-1, respectively. These findings could prove and potentiate the nephroprotective activities of the BNS extract in the range of the given doses. Further clinical studies are highly recommended for confirming the nephroprotection efficiency of the B. nigra sprout.

Hepatoprotective outcome of Silymarin against CCl4 induced hepatotoxicity in rabbit model

For centuries, medicinal plants have been used to treat human and animal ailments. Recent research indicated Silymarin as commonly employed antioxidant, hepatoprotective, cardioprotective, antiviral and antifibrotic. Anti-oxidant properties are believed to be responsible for its hepatoprotective effect. In this research, 46 rabbits were utilized in total. Each rabbit was separated into 04 groups: Group A (n=13) served as control and received neither Silymarin nor CCl4 treatment. Group B (n=13) was given 100 mg/Kg CCl4 as treatment. CCl4 and Silymarin were administered to Groups C and D (n=10), respectively. Using commercially available assays, the parameters Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), Alkaline Phosphatase (ALP), total bilirubin, direct bilirubin, and serum urea were determined for each animal. Multiple comparisons between each of the four categories were analyzed statistically. Administration of Silymarin in CCl4-induced liver toxicity improved all parameters significantly (P&lt;0.05). The AST Mean ± SE of Groups A, B, C and D was 73.98 ± 2.22, 137.00 ± 4.22, 120.90 ± 3.00 and 95.43 ± 2.85 respectively. Groups A, B, C, and D had respective ALT Mean SE values of 44.51+ 2.64, 99.47 + 3.19, 74.60 + 3.20, and 54.60 + 3.20. Total Bilirubin for Groups A, B, C, and D were 0.622 + 0.023, 1.302 + 0.025, 0.959 + 0.033, and 0.765 + 0.024, respectively. 100 mg Silymarin demonstrated more significant results than 50 mg Silymarin. In conclusion, Silymarin has hepatoprotective, anti-fibrotic, and anti-cirrhosis properties. It is well-tolerated and efficacious antidote for CCl4-induced hepatotoxicity

D-Limonene Alleviates Oxidative Stress Injury of the Testis Induced by Arsenic in Rat.

Long-term exposure to arsenic can lead to testicular damage and lower sperm quality in males, which is mediated by increased arsenic-induced oxidative stress and other damage mechanisms. D-Limonene, which is rich in oranges, lemons, oranges, grapes and other natural fruits, can relieve doxorubicin (DOX)-induced kidney injury and CCL4-induced cardiac toxicity by inhibiting oxidative stress and inflammatory response. The antioxidant and anti-inflammatory properties of D-limonene motivate us to further explore whether it can reduce arsenic-induced testicular injury. To verify this scientific hypothesis, testicular pathology, testicular oxidative stress levels and sperm motility were determined after intervention with D-limonene in rats chronically exposed to arsenic. As expected, long-term arsenic exposure caused testicular tissue structure disturbances, increased levels of oxidative stress, and decreased sperm activation, all of which were significantly inhibited due to treatment with D-limonene. In conclusion, our data reveal a previously unproven beneficial effect of D-limonene, namely that D-limonene can inhibit arsenic-induced testicular injury, and also provide theoretical and experimental basis for the application of D-limonene in the treatment of arsenic-induced testicular injury.

Spectroscopic characterization of eupalitin-3-O-β-D-galactopyranoside from Boerhavia procumbens: In vivo hepato-protective potential in rat model

The liver is one of the most important organs responsible for detoxifying biomolecules and xenobiotics. Herein, we report the isolation, characterization, and hepatoprotective effect of the Boerhavia procumbens-derived eupalitin-3-O-β-D-galactopyranoside (EGP) compound. The structure of the EGP compound was deduced by using NMR spectroscopic techniques and mass spectrometry. The EGP hepatoprotective activities were evaluated with HepG2 cell viability and LDH assays in vitro, and CCl4-induced toxicity was investigated in vivo in the rat model. Compared to the CCl4-treated group, cells exposed to the EGP compound at 200 µg/ml showed increased cell viability (60.52 ± 1.22 %) and decreased LDH levels (23.81 ± 1.89 U/ml). The serum levels of SGPT, SGOT, ALP, and total bilirubin in the CCl4-treated group were substantially higher than those in the control group (64 ± 1.89 U/ml, 86 ± 1.47 U/ml, 252.6 ± 2.96 U/ml, and 5.45 ± 0.32 mg/dl, respectively). When compared to animals treated with CCl4 alone, the EGP compound's in vivo hepatoprotective effect at 60 mg/kg with CCl4 significantly (p < 0.01) decreased the levels of SGPT and SGOT (26 ± 1.34 U/ml and 42.92 ± 1.6 U/ml) respectively. Furthermore, our histological study showed a significant response in restoring and maintaining the normal morphological appearance of the liver. Thus, our results show that the EGP compound is a promising and novel lead molecule for better hepatotoxicity control and therapy.

Evaluation of Cardiac Profile in CCl4 Induced Toxicity in Albino Rats

The use of consumer and fumigant products like CCl4 has been phased down, leaving only industrial usage. It is extremely harmful to one's health. It's also one of the most toxic substances in vital organs like the lungs, kidneys, liver, heart, and brain. Objective: To evaluate the cardiac profile in CCl4-induced toxicity in albino rats. Methods: The research was conducted at animal home of Department of Zoology, University of Okara. The targeted victims were albino rats. There were two types of groups created: control group and experimental group. The rats were fed 30 percent diluted carbon tetrachloride with normal saline as a control group to see if it had an adverse effect on their cardiac profile. A 12-day trek was used to accomplish this. After 12 days, samples were taken or dissected to assess serum Creatine Kinase (CPK), (CK-MB), and (LDH). The samples were analyzed by a machine called Micro-Lab 300 after they were taken by puncturing the Rats' hearts. Results: Abnormal increased level for Creatine Kinase (CPK) (199.20 ± 1.93) was observed after the administration of CCl4 compared to normal control (71.60 ± 4.04). When CCl4 was injected, the level of CK-MB was abnormally high (34.00 ± 1.21) compared to the normal control (16.00± .84). The level of LDH increased abnormally (291.60 ± 5.01) when CCl4 was given, compared to the normal control (250.20± 2.16). Conclusions: The levels of Creatine Kinase (CPK), CK-MB, and LDH were found to be greater than normal, showing that CCl4 is hazardous to rats cardiac profile.

Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats

Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1β, IL-6, IL-10, TNF-α, and TGF-β genes. Gas Chromatography-Mass Spectroscopy (GC–MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-β, IL-1 β, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.