CCl4-induced Hepatotoxicity Research Articles

BIOCHEMICAL AND HISTOLOGICAL STUDY OF THREE DIFFERENT MULTIHERBAL COMPOSITIONS ON HEPATOXICITY INDUCED BY CARBON TETRA CHLORIDE (CCL4) IN ALBINO RATS

Objective: The present study aimed to evaluate the hepatoprotective activity of three different types of multiherbal formulations in comparison to standard drug (Silymarin). Methods: Five hepatoprotective plants were chosen to make three different kinds of formulations, as mentioned in the materials and methods. These five selected herbs were chosen based on previous researches or reviews on hepatoprotective herbs. For the present study, two different groups of rats were made: the control group and the experimental group. The experimental group was further divided into five subgroups. Hepatotoxicity was induced by a single oral dose (1.5 ml/kg) of CCl4. After this, all rats were treated with different formulations and standard drug (silymarin) according to their groups. Samples for biochemical and histopathological (liver sample) examinations were collected on the fixed schedules (07th, 14th, and 21st d). Results: Biochemical parameters like SGPT, SGOT, and ALP were elevated due to CCl4-induced hepatotoxicity, and after treatment, they were recouped to normal significantly (P<0.001) by the treatment of formulation-I. On the other hand, decreased serum proteins like total, albumin, and globulin were increased to be normal (P<0.01) with the treatment of formulation-I. The histopathological study also supported the final results of the biochemical analysis. The damaged hepatocellular structures were repaired by the F-I formulation better than other formulations. Conclusion: The final results suggested that Formulation-I is a better healer than other formulations (F-II and F-III). It was thus concluded in the present study that formulation-I has better hepatoprotective activity than formulation-II and formulation-III.

Protective Effects of Ethyl Acetate Extract from <i>Ficus Carica L.</i> Leaves Against CCl4-Induced Hepatotoxicity In Vitro and In Vivo

Protective Effects of Ethyl Acetate Extract from <i>Ficus Carica L.</i> Leaves Against CCl4-Induced Hepatotoxicity In Vitro and In Vivo

DNA interaction of selected tetrahydropyrimidine and its effects against CCl4-induced hepatotoxicity in vivo: Part II.

Tetrahydropyrimidine (compound A = methyl 4-[4'-(heptyloxy)-3'-methoxyphenyl]-1,6-dimethyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate) was chosen for in vivo studies after exhibiting noteworthy in vitro activity against the K562 and MDA-MB-231 cell lines, with IC50 values of 9.20 ± 0.14 µM and 12.76 ± 1.93 µM, respectively. According to experimental (fluorescence titration, viscosity, and differential scanning calorimetry) results, A interacts with DNA via the minor groove. In vivo, acute oral toxicity studies in Wistar albino rats proved no noticeable symptoms of either toxicity or death during the follow-up period. Genotoxic and antigenotoxic studies at three different concentrations of A (5, 10, and 20 mg/kg of body weight) in Wistar albino rats showed that the dose of 5 mg/kg body weight did not cause DNA damage and had a remarkable DNA protective activity against CCl4-induced DNA damage, with a percentage reduction of 78.7%. It is also important to note that, under the investigated concentrations of A, liver damage is not observed. Considering all experimental outcomes realized under various in vivo investigations (acute oral toxicity, genotoxicity, antigenotoxicity, and biochemical tests), compound A could be a promising candidate for further clinical testing.

Levisticum officinale extract protects against CCl4-induced hepatotoxicity through anti-inflammatory, anti-fibrotic, and antioxidant properties in rats

Objective: To investigate the hepatoprotective effects of Levisticum officinale extract on CCl4-induced hepatotoxicity. Methods: Different doses of Levisticum officinale extract were given orally to rats for 10 days, then rats received a single dose of CCl4 (2.5 mL/kg, 50% v/v in liquid paraffin). Biochemical and histopathological assays were performed to assess the effects of the extract on liver function and architecture. Moreover, antioxidant and oxidative markers as well as inflammatory and fibrotic indicators were measured. Results: Pretreatment with Levisticum officinale extract significantly mitigated CCl4-induced damage to liver structure, improved serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea, total bilirubin, and total protein, enhanced glutathione content and superoxide dismutase and catalase activities in the liver, as well as decreased plasma and hepatic malondialdehyde levels. Immunohistochemical results demonstrated that the extract reduced Ki-67 and α-SMA expression and Masson’s trichrome staining revealed decreased liver collagen in rats treated with Levisticum officinale extract. Moreover, Levisticum officinale extract markedly decreased the gene expressions of TNF-α, 1L-6, TGF-β1, MCP-1, and COX-2. Conclusions: Levisticum officinale extract exerts hepatoprotective effects on CCl4-induced hepatotoxicity through antioxidant, anti-inflammatory, and anti-fibrotic activities.

Phyto- and biochemical study on cape gooseberry (physalis peruviana L.) extract incorporated with metal nanoparticles against hepatic injury induced in rats

The study aimed to investigate the role of metal nanoparticles (M-NPs) in improving the efficiency of Physalis peruviana (Cape gooseberry) juice, which is rich in numerous important therapeutic phytochemicals. Therefore, it was subsequently studied against chemically-induced toxicity in rats. The present study demonstrated that C. gooseberry juice was used for the biosynthesis of silver (Ag-NPs) and zinc oxide nanoparticles (ZnO-NPs). The ZnO-C. gooseberry nano-extract exhibited higher in vitro biological activities compared to the other extracts. It was also found to be safer when administered orally. Moreover, it demonstrated a greater ameliorative effect against hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. It restored the integrity of the liver tissue by increasing levels of antioxidant enzymes and reducing the inflammatory markers significantly (p ≤ 0.05). The study found that the ZnO-C. gooseberry nano-extract demonstrated greater efficacy in combating CCl4-induced hepatotoxicity compared to the other extracts.

Antioxidant and Hepatoprotective Activity of an Extract from the Overground Parts of Phlomis russeliana Lag. ex Benth

An evaluation of the possible hepatotoxicity/hepatoprotective effects of a defatted extract of the above ground parts of Phlomis russeliana was conducted in vitro and in vivo. The extract was tested in vitro on hepatocytes alone and in a carbon tetrachloride (CCl4)-bioactivation model. The same toxic substance was used for the in vivo evaluation on old Wistar rats. The extract was standardised via high performance liquid chromatography (HPLC) by the quantification of total flavonoids and verbascoside. Gallic acid equivalents were used to express the content of total phenolic compounds. The identification of flavonoids in this species was undertaken for the first time. The extract was not statistically hepatotoxic in vitro on the isolated rat hepatocytes. In the CCl4-induced hepatotoxicity model, the extract had a hepatoprotective effect, which was concentration-dependant (the highest at 50 µg/mL). An in vivo study on old rats confirmed the observed antioxidant and hepatoprotective effects. The histological findings were favourable for the rats, given the extract and CCl4 in combination. They had an unchanged organ structure, which is commensurable with these animals, treated with a combination of CCl4 and silymarin.

Evaluation of hematoprotective, hepatoprotective, and anti-inflammatory potentials of chia seed (Salvia hispanica L.) extract in rats

This study was conducted to evaluate the effects of chia seed extract on CCl4-induced hepatotoxicity, hematological profile, and carrageenan-induced inflammation in rats. Water-ethanol-acetone extract of chia seeds at the doses of 200 and 400 mg/kg body weight/day were applied to evaluate the comparative protective roles. Hematological profile and serum biochemical parameters were measured to evaluate the hematoprotective, and hepatoprotective effects of chia seed extract. Paw thickness and motility level were assessed at 0, 1, 3, 5, and 7 h after sub-planter injection of carrageenan to evaluate the anti-inflammatory potential. Tissue histopathology was performed in both cases. Chia seed extract reduced the elevated level of serum AST and ALT significantly in a dose-dependent manner following intra-peritoneal injection of CCl4. Histopathological study of the liver tissue exhibited acute impairment of the hepatocytes and liver parenchyma following CCl4 exposure, which was markedly regenerated by the chia seed extract treatment. Protective effects of the extracts were also evidenced by the RBC count, Hb (%), PCV (%), ESR, and neutrophil count. Chia seed extract was found to inhibit the carrageenan-induced paw edema and increase motility level in a dose-oriented fashion. Histological examination of the paw tissue revealed severe inflammation characterized by massive infiltration of inflammatory cells in the carrageenan group, which was significantly reduced by chia seed extract treatment. The higher dose of chia seed extract showed significant increases in bodyweight gain and feed efficiency ratio but decrease in visceral fat deposition. These results suggest that chia seeds possess potentials for hematoprotective, hepatoprotective, and anti-inflammatory activities.

<i>In Vivo</i> Hepatoprotective Activity of Hydroalcohol Extract of <i>Gyrocarpus asiaticus</i> Willd and <i>Lactuca runcinata</i> DC

Objective: Investigation of hepatoprotective activity of Gyrocarpus asiaticus Willd (GA) and Lactuca runcinata DC (LR) prepared by hydroalcohol extraction. Methodology: Albino rats were used for the in vivo experiments for the determination of oral acute toxicity study. For these experiments, 6 groups were created of which 5 groups were for each plant extract and 1 group for control. A total of 11 groups were made for the toxicity study. Each group required 2 albino mice. Different doses of 0.025, 0.2, 0.5, 2, and 5 gm/kg body weight were administered orally for each plant extract. For the control group, these were administered with distilled water. For hepatoprotective activity, albino rats were randomly divided into 5 (control, toxic, standard, 2 samples) groups, and 4 animals were randomly divided into each group. For 2 plants, a total of 7 groups were made. 5% gum acacia was used as the vehicle. For induced hepatotoxicity CCl4 and as a standard drug silymarin was used. Result and Discussion: Plant extracts did not show any toxicity, and no histopathological changes were seen in the liver, kidney, or lungs due to toxicity. In the study of GA Willd and LR DC extract prepared by hydroalcohol solution, there was evidence of protection against CCl4-induced hepatotoxicity in the Histopathological study of the liver of albino rats. Conclusion: Hydroalcohol extract of LR DC and GA Willd shows no oral acute toxicity and LR DC shows no significant hepatoprotective activity but GA Willd shows significant hepatoprotective activity

Ethanolic Extract of Mangifera indica Protects against CCl4-Induced Hepatotoxicity via Antioxidant Capabilities in Albino Rats.

To investigate the antioxidant and hepatoprotective effects of ethanolic Mangifera indica (M. indica) seed extract on carbon tetrachloride (CCl4)-induced hepatotoxicity in albino rats. Forty-eight albino rats weighing (100-150 g) were used for hepatoprotective and toxicity experiments. Antioxidant activity was determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The toxicity of M. indica seeds on the liver was evaluated by examining wellness parameters, body weight, and liver histological sections. The protective effects of 50 mg/kg and 100 mg/kg of seed extract on CCl4-induced hepatotoxicity were investigated by evaluating hematological, renal, and liver function parameters, body weight, and liver histological sections. The antioxidant activity of the M. indica ethanolic extract was (92 ± 0.03 RSA %) compared with (91 ± 0.01 RSA %) of propyl gallate, and the IC50 was (8.3 ± 0.01 µg/ml) and (14.1 ± 0.01 µg/ml). No changes were observed in the health indicators, body weights, and liver histological sections following oral administration of 50 mg/kg and 100 mg/kg of M. indica seed extracts. Treatment with M. indica seed extract significantly reduced alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), blood sugar, and urea levels compared with those in the CCl4-treated group. The IC50 of the M. indica ethanolic extract was 8.3 µg/ml, and the M. indica extract is a potential source of natural antioxidants that protect against CCl4-induced hepatotoxicity.

Preliminary evaluation of hepatoprotective potential of Maytenus emarginata Willd. (Celastraceae) plant and callus extracts against CCl4-induced hepatotoxicity in male Wistar albino rats

Preliminary evaluation of hepatoprotective potential of Maytenus emarginata Willd. (Celastraceae) plant and callus extracts against CCl4-induced hepatotoxicity in male Wistar albino rats

Comparative Study of Nanosilymarin Loaded on Chitosan versus Free Silymarin in CCl4-Induced Hepatotoxicity in Female Rats

Comparative Study of Nanosilymarin Loaded on Chitosan versus Free Silymarin in CCl4-Induced Hepatotoxicity in Female Rats

Anti-oxidative constituents of Musa balbisiana Colla fruit extract and evaluation of hepatoprotective activity in CCl4-induced hepatotoxicity in Swiss albino mice

Carbon tetrachloride is employed to induce hepatotoxicity in experimental animals to mimic oxidative stress caused by several factors in humans and impair liver functions and lead to hepatic damage. Fruits of Musa balbisiana Colla are rich in bioactive compounds and hold therapeutic and nutritional worth. This current study aims to explore the phytochemical constituents, antioxidant effects, and hepatoprotective activity of a methanolic extract derived from the unripe fruit pulp of M. balbisiana Colla via phytochemical screening, evaluation of antioxidant activity, in vivo experiments in Swiss albino mice through monitoring of the body and the liver weight, estimation of hepatic biomarkers, enzymes, malondialdehyde (MDA), and cytokines along with immunohistochemical and histopathological study. The methanolic fruit extract administration minimized hepatic biomarker and MDA levels along with the cytokines and also elevated superoxide dismutase, catalase, plus glutathione content compared to the hepatotoxic group (p < 0.05). Immunohistochemical findings and histopathological examinations of the liver tissues from methanolic extract-treated mice displayed the down regulation of transforming growth factor beta in hepatic parenchymal tissues and re-establishment of standard structural attributes of hepatic tissue. The outcomes of our research illustrate that the methanolic fruit extract of M. balbisiana Colla administration assists in hepatotoxicity attenuation.

Hepatoprotective efficacy of Leptadenia reticulata methanolic leaf extract in albino rats exposed to CCl4-induced hepatotoxicity

Hepatoprotective efficacy of Leptadenia reticulata methanolic leaf extract in albino rats exposed to CCl4-induced hepatotoxicity

HEPATOPROTECTIVE ACTIVITY OF FRUIT AND LEAF EXTRACTS OF FICUS CARICA AND FICUS BENGHALENSIS IN EXPERIMENTAL RATS

Ficus plants have traditionally been used as potential remedies for treating various diseases. Hepatotoxicity is one of the severe threats to human health which must be adequately cured. The study was planned to investigate the hepato-protective potential of methanolic extracts of fruit and leaves of Ficus carica and Ficus benghalensis against carbon tetrachloride (CCl4)-induced hepatotoxicity in an experimental rat model. The study was planned using a randomized control design (RCD). The study included 6 groups of animals (n= 5 per group) having average body weight (230±20 g), out of which 5 groups were treated with CCl4 (15 µL kg-1 body weight), and the remaining one was left as healthy control. Four of the five CCl4-treated groups were administered individually with fruit and leaf extracts (25 mg kg-1 body weight) of F. carica and F. benghalensis, while the fifth was left as CCl4-treated control. The total serum bilirubin (TSB), total serum protein (TSP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels of the control group during the treatment period ranged from 0.54±0.16 to 0.59±0.15 mgdL-1, 8.56±0.73 to 8.66±0.75 gdL-1, 46.00±21.41 to 49.41±22.68 UL-1, 41.6±13.99 to 44.41±13.16 UL-1, and 139.80±28.72 to 145.62±28.82 UL-1, respectively. CCl4 administration significantly (p<0.05) increased the TSB, ALT, AST, and ALP levels in the range of 1.48±0.30-2.30±0.19 mgdL-1, 147.6±34.22 to 233.81±14.94 UL-1, 118.8±15.88 to 167.8±16.4143 UL-1, and 213.8±21.46 to 260±26.664 UL-1, respectively. The elevated TSB, ALT, AST, and ALP levels were significantly (p<0.05) decreased after F. carica and F. benghalens extract treatment to 1.06±0.15-1.70±0.21 mgdL-1, 115.00±28.19-190.21±25.68 UL-1, 89.8±16.29-111.8±23.81 UL-1, and 195.38±42.29-218.4±35.02 UL-1 respectively. Moreover, TSP level was significantly decreased after CCl4 administration and improved after extract treatment. It was concluded that methanolic extract from the leaf and fruit of both F. benghalensis and F. carica protects against CCl4-induced hepatotoxicity in rats. Keywords: Hepatoprotective potential, Ficus carica, Ficus benghalensis, Hepatic damage, Experimental rat model

An analysis of Heptoprotective effects of plant extract on albino rats by Deep Learning analysis using ResNet and VGG16 algorithms

The hepatoprotective and anti-inflammatory effects of Terminalia catappa L. and Pergularia daemia hydroalcoholic extracts in albino rats with CCl4-induced liver damage (HAETC and HAEPD, respectively). The extracts significantly reduced the harm induced by CCl4 when given orally at a dosage of 200mg/kg. They also showed strong hepatoprotective and antioxidant properties. Wistar albino rats in good health were divided into seven groups, each with six animals. Group I acted as the control and received no treatment, whereas Group II was given 30% CCl4 (1ml/kg, intraperitoneally) to cause hepatotoxicity. After administering Silymarin (25 mg/kg, orally) as per protocol, Group III underwent CCl4 therapy. The CCl4-induced rats showed significant reductions in antioxidant enzymes like SOD, catalase, glutathione peroxidase (GPX), and glutathione-S-transferase (GST), as well as increases in serum marker enzymes like SGOT, SGPT, alkaline phosphatase (ALK), ACP, LDH, and lipid peroxidation (LPO) activity. However, rats given HAEPD and HAETC showed significant improvements, returning these parameters to levels that are almost normal (P 0.001).The hepatoprotective and antioxidant benefits of Terminalia catappa L. (HAETC) and Pergularia daemia (HAEPD) against CCl4-induced hepatotoxicity in rats were further validated by histopathological analysis of liver tissues. It encourages the use of pre-trained CNN architectures, such as VGG16 and ResNet (Residual Network), in the proposed method, which uses convolutional neural networks (CNNs) for histopathological image analysis to assess the hepatoprotective properties of Pergularia daemia and Terminalia catappa L. leaf extracts against CCl4-induced hepatotoxicity. These well-known CNN models may be modified for precise and effective histopathological image interpretation, assisting in the evaluation of the impact of plant extracts on liver health.

Decalepis hamiltonii root fraction alleviates CCl4 hepatotoxicity in a rat model

BackgroundDecalepis hamiltonii (D. hamiltonii) is Indian folk medicine in herbal preparations, to reduce appetite, and cures dysentery, bronchitis, uterine hemorrhage, and other ailments. ObjectiveThe current investigation focused on the hepatoprotective effect of D. hamiltonii roots fractions against liver damage. Materials and methodsThe current research discussed the fraction from D. hamiltonii root extracts was used. Male Wistar rats (albino strain) were grouped into 4 distinct groups of six animals each. Group I: plain water and vehicle whereas Group II (CCl4 control): CCl4 (1 ml/kg, 20 % v/v in olive oil) over 7 days and vehicle; Over 7 days, Group III received Silymarin 100 mg/kg/day and tap water with 20 % v/v of CCl4, whereas Group IV (treatment group) received DHE 50 mg/kg/day, 100 mg/kg/day, and water. Assessment of biochemical parameters, Mitochondrial modulation, gene expression analysis, and RT-PCR, was used to estimate the protective action of DHEF in CCl4-intoxicated rats. ResultsThe administration of CCl4 increased levels of total bilirubin (0.63 ± 0.97 mg/dl) plasma amino transferases (110.36 ± 1.13 U/L, 86.56 ± 2.41 U/L and 1.51 ± 1.36 mg/dl respectively) which were mitigated by D. hamiltonii treatment. Activity like Lipid peroxidation and content of nitric oxide also augmented, while the antioxidant action measured by GSH (9.64 ± 0.18 U/mg protein), SOD (3.69 ± 0.22 U/mg protein), and CAT (1.47 ± 0.01 U/mg protein) was reduced. Decalepis hamiltonii root provided substantial restoration of GSH (14.92 ± 0.04 nmol/gm protein), SOD (4.20 ± 0.18 U/mg protein), and CAT (2.71 ± 0.04 U/mg protein) levels. In addition, the acute phase reactants stimulated by CCl4 administration enhanced mRNA expressions of IL-6, IL-10, TNF-a, NF-κβ, and COX-2, which were enhanced by D. hamiltonii treatment. ConclusionsIn summary, DHEF protects the liver against CCl4-induced damage, possibly by mitochondrial modulation mechanism. These findings indicate that D. hamiltonii significantly moderates oxidative stress of CCl4-induced hepatotoxicity.

Investigating the Anti-inflammatory Effects of Rutin in Carbon Tetrachloride-induced Hepatotoxicity: Role of TLR4/MyD88/NFκB Signaling Pathway Modulation

Objectives Rutin protects and stabilizes hepatocytes and is used to treat hepatitis, liver cirrhosis, and other diseases. However, there is little evidence to suggest that Rutin is associated with CCl4-induced hepatotoxicity. In this study, we investigated the effects of Rutin on CCl4-induced liver inflammation and discussed in vivo and in vitro mechanisms. Materials and Methods CCl4 was used to induce liver inflammation, and Rutin was used for intervention in mice. Then the body weight, liver weight, and liver inflammation of all mice were measured. Western blotting and RT-PCR were used to assess TLR4/MyD88/NFκB inflammation signaling pathways and inflammatory gene expression. Finally, TLR4 was activated in primary hepatocytes to verify the above signal pathways. Findings CCl4 mice developed liver function damage and liver inflammation. Further investigations showed that the inhibitory effects of Si on inflammation were mediated by TLR4/MyD88/NFκB inflammation signaling pathways inhibition. Primary hepatocyte studies also confirmed the participation of these signaling pathways and proteins. Significance Rutin improved CCl4-induced liver inflammation. Such mechanisms may be related to TLR4/MyD88/NFκB inflammation signaling pathways.

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<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

Cakes fortified with papaya seeds effectively protects against CCl4-induced immunotoxicity

Maintaining a robust immune system and safeguarding the liver from toxins are crucial for overall health. The study aimed to investigate the immunostimulant effects of papaya seed-enriched cakes (CPS) in countering carbon tetrachloride (CCl4)-induced immunocytotoxicity in rats (n = 48). The rats were divided into six groups (8 each): a control group (Group 1), rats fed cakes containing 15% papaya seeds (Group 2 — CPS), rats exposed only to CCl4 (Group 3 — CCl4), rats injected with CCl4 and administered silymarin (Group 4 — CCl4 + S), rats receiving both CCl4 and cakes with papaya seeds (Group 5 — CCl4 + CPS), and rats receiving both CCl4 and silymarin with papaya seed-enriched cakes (Group 6 — CCl4 + CPS + S). HPLC analysis of papaya seeds revealed the presence of ten polyphenol compounds, with quercetin, apigenin, and catechin identified as major flavonoids, along with pyrogallol, ellagic, and gallic acid as predominant phenolic acids. These compounds displayed potent antioxidant activity, attributed to the seeds’ high total phenolic and flavonoid content. The administration of CCl4 significantly affected hematological parameters, liver enzymes, hepatic oxidative stress, levels of TNF-α, IL-6, IgG, as well as IgM. However, rats fed with CPS exhibited mitigation of CCl4-induced toxic effects on hematological parameters and hepatotoxicity. CPS consumption enhanced the antioxidant system, improved inflammatory markers, and immune parameters, restoring them to normal levels. Histopathological analysis confirmed CPS’s ability to reduce CCl4-induced hepatocellular necrosis. Immunohistochemical assessment further revealed reduced immunoreactivity against cleaved caspase-3 expression and increased COX2 immunoreactivity, indicating hepatocellular regeneration in CPS. The combination of CPS and silymarin demonstrated even more notable improvements, suggesting augmented protective impacts against CCl4-induced immunosuppression and hepatotoxicity. In conclusion, CPS exhibited antioxidant properties and effectively protected against CCl4-induced immunotoxicity and hepatotoxicity, with additional benefits observed when combined with silymarin. These findings emphasize the potential health advantages of incorporating papaya seeds into food products, promoting immune system health, and safeguarding against liver damage induced by hazardous agents like CCl4.

Economic Importance of Garcinia Kola: Evidences of Shielding Outcome Against Carbon Tetrachloride-Induced Kidney Toxicity in Experimental Models

Introduction: The aim of the study was to evaluate the hepatoprotective effect of aqueous extract of Garcinia kola) seeds on carbon tetrachloride (CCl4) induced liver damage in adult Wistar rats. Thirty adult Wistar rats weighing between 65-145g were randomly divided into six groups of 5 rats each. Group A (control) rats were orally administered with 5ml/kg body weight of distilled water daily for 2 weeks, group B rats were administered distilled water orally daily for 2 weeks (volume per body weight) and carbon tetrachloride (CCl4) 0.4 m1/kg intraperitonially as a single application on day 14 of the experiment. Group C rats were administered 100 mg of silymarin / kg body weight once daily for 2 weeks followed by a single dose of CCl4 (0.4 m1) on day 14 of the experiment. Group D rats were administered 400 mg aqueous extract bitter kola (Garcinia kola) / kg body weight orally once daily for 2 weeks. Group E and F rats were administered 400 mg and 200 mg aqueous extract bitter kola (Garcinia kola) seed) orally once daily for 2 weeks followed by a single dose of CCl4 (0.4 m1) on day 14 respectively. At the end of the experiment. Garcinia kola seed aqueous extract caused significant decrease in the aspartate aminotransferase (AST) levels in the serum of the extract treated groups. Histopathological examinations revealed distortion of histoarchitecture such as, sinusoidal congestion, necrosis, steatosis and fibrosis was observed in group B. The administration of aqueous extract of Garcinia kola seed remarkably inhibited histoarchitectural distortion induced by CCl4 administration. Effects of the extract at dose of 200mg/kg was comparable to the reference drug. Garcinia kola aqueous seed extract showed a remarkable hepatoprotective and antioxidant activity against CCl4 induced hepatotoxicity as observed from the serum marker enzymes and antioxidant levels in liver tissues. CCl4 induced a significant rise in AST, ALT, and ALP with an increase of superoxide dismutase (SOD), catalase (CAT) and reduction lipid peroxidation (MDA). Treatment of the rats with the extract significantly (p<0.05) altered serum marker enzymes and antioxidant levels to near normal compared with CCl4- treated rats (group B). The activity of the extract at dose of 400mg/kg (group F) was comparable to the standard drug confirmed by histopathological examinations of liver sections. Conclusion: Garcinia kola aqueous extract has hepatoprotective and antioxidant properties against CCl4-induced hepatotoxicity in Wistar rats.