Hepatic Damage In Rats Research Articles

Protective effect of aqueous fruit extract of Mondia whitei against cadmium-induced hepatotoxicity in rats

Introduction: Mondia whitei (Hook.f.) Skeels is rich in antioxidant activity and is known for its nutritional and medicinal uses. This study evaluated the protective effect of M. whitei fruit against cadmium-induced hepatic damage in rats. Methods: Twenty-five albino (Wistar strain) rats were randomly assigned into five equal groups. Rats in group I served as control, rats in group II were intoxicated with 5 mg/kg body weight (b.w.) cadmium chloride (CdCl2 ) for 5 days via an oral route, while groups III, IV, and V were respectively administered with 5 mg/kg b.w. CdCl2 for 5 days co-treated with 70 mg/kg b.w silymarin, 250 and 500 mg/kg b.w. of aqueous fruit extract of M. whitei (AEMW) for 7 days. Results: Cadmium caused a significant (P<0.05) increase in the concentration of cadmium in the liver as well as liver function markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and bilirubin. In addition, a significant (P<0.05) elevation in the level of malondialdehyde (MDA) and a reduction in the nitric oxide (NO) and antioxidant status were noted in the CdCl2 -exposed rats; hepatic degeneration and congested portal area were also noted. These changes were, however, reduced in the cadmium-intoxicated rats co-treated with silymarin, 250 mg/kg or 500 mg/kg AEMW. Conclusion: Our result suggests that AEMW exerts protective effects against CdCl2 -induced hepatic damage in rats, and this might be due to the presence of phytochemicals in the plant capable of scavenging oxidative stress caused by cadmium.

High Fat Diet and Low Dose Streptozotocin Induced Diabetic Dyslipidaemia and Hepatic Damage in Rats

The objective of the present study was to validate a rat model of diabetic dyslipidaemia along with hepatic damage by High fat diet and low dose streptozotocin combination that resembles the natural history of metabolic syndrome in humans. Male and Female Sprague Dawley rats were divided into 2 groups. One group of rats fed with high fat diet and other group was fed with normal pellet diet for a period of 2 weeks followed by streptozotocin administration on 15th day. Body weight of the animals was measured on day 0, 14 and 21, also post 1 week of the streptozotocin administration the blood glucose, serum lipid, liver, kidney markers and insulin levels were measured. The high fat diet fed animals had exhibited a significant increase in body weight post two weeks of HFD feeding, but the body weight was reduced post 1 week of streptozotocin intervention due to metabolic disruption caused by STZ. The HFD group animals exhibited significant increase in blood glucose, serum total cholesterol, triglycerides, LDL, VLDL. Similarly, a significant decrease in HDL and serum insulin levels were observed as compared to the NPD fed animals. Further the HFD group animals had shown significant elevation of the liver function enzymes such as ALT and ALP levels as compared to the NPD fed animals. The present study confirms the experimental induction of diabetic dyslipidaemia along with hepatic damage which serves as an ideal model for metabolic syndrome along with hepatic cirrhosis which would useful for evaluating the therapeutic agents against type 2 diabetes, hyperlipidaemia and hepatic cirrhosis.

Lipid composition and oxidative changes in diabetes and alcoholic diabetes rats

BackgroundThe investigating of study was expected to the lipid composition of diabetes and alcoholic diabetes in plasma and erythrocyte membrane biochemical profile in rats. Diabetic male Wistar Streptozotocin (STZ)-induced rats were used experimental models. Control rats (C) were maintained group I, received glucose (i.e., caloric equivalent), diabetic induced rats (STZ) group II, and group III alcoholic treated and IV diabetic and alcoholic treated rats which received 20 % (v/v) alcohol in water, administered through stomach tube (5 g/kg body weight/day). ResultsSTZ-induced diabetic hepatic damage in rats was observed which leads to the increased plasma lipid peroxidation, nitrate and nitrite levels. Diabetic and administration alcohol rats also suggestively lesser the activities of antioxidants, glutathione peroxidase, glutathione S-transferase, superoxide dismutase, catalase and reduced glutathione when related with control rats (group I). Plasma enzymes are normal levels and renovate the enzymic and non-enzymatic antioxidants level in experimental groups. ConclusionThe present data point out that the nitric oxide scavenging levels increased and may possibly protect and adjacent to oxidative stress and free radicals in diabetic hepatopathy rats and histopathological studies were identified in regular hepatic cortex of Group II, III and IV of animals with diabetes, alcoholic and alcohol-induced diabetes rats.

Protective effect of Ceiba pentandra (L) Gaertn on CCl4-induced oxidative stress and liver damage in rats

BackgroundCeiba pentandra (L.) Gaertn, popularly known as the white silk-cotton tree and popularly used in Chinese and Indian traditional medicine. The bark is used to treat diarrhea, pain, fever, cardiac problems, asthma, and gastrointestinal problems. The present study aimed to evaluate the hepatoprotective and antioxidant effects of ethanol extract of C. pentandra bark (EECP-BK) against CCl4-induced hepatic damage in rats. MethodsPreliminary phytochemical analysis was performed to identify the bioactive compounds. CCl4 (40 mM) induced enzymatic changes at HepG2 cells were adopted for the in-vitro model. HepG2 cells were pretreated with EECP-BK (25, 50, 100, and 200 µg/ml) and standard (silymarin 12.5 µg/ml) respectively. Rat model of CCl4-induced liver damage for adopted for the in-vivo model. Rats were pretreated orally with EECP-BK 200 & 400 mg/kg and standard (silymarin 100 mg/kg) for 7 days. Rats were injected with 1 ml/kg of 50% CCl4 on day 8 to induce hepatic damage and were observed for antioxidant levels and serum biomarkers. In addition, in-silico studies have been performed to explore the binding properties of compounds from EECP-BK with tumor necrosis factor-alpha converting enzyme (TACE) targeting hepatic inflammation ResultsThe phytochemical analysis confirmed the presence of glycoside, steroids, phenols, tannins, and saponins. EECP-BK 200 µg/ml showed the highest protection against CCl4 in HepG2 cells. Similarly, silymarin 12.5 µg/ml showed good protection against CCl4. In rats, EECP-BK up to 2000 mg/kg did produce any toxic signs or mortality. CCl4 injection in rats showed elevated liver enzymatic and bilirubin levels and causes liver damage. It also decreased the SOD, CAT, and GSH levels. Pre-treatment with EECP-BK 400 mg/kg showed a significant reduction in SGPT, SGOT, ALP, and total bilirubin levels and increased SOD, CAT, and GSH levels. Similar results were observed with, silymarin treatment also. Furthermore, EECP-BK showed protection over hepatocyte necrosis induced by CCl4 in rats which is evident by histopathology. Molecular docking studies revealed that acacetin 7-rutinoside binds favorably with the active site of TACE with a binding affinity of -8.8 kJ/mol. ConclusionOur findings supported the antioxidative capability of EECP-BK by showing that it protected the liver from CCl4-induced hepatic damage. Additional research is needed to determine its safety profile and to find its molecular mechanism for therapeutic application.

The Concurrent Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells on Gentamycin-induced Hepatorenal Toxicity in Rats.

Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin- induced hepatorenal damage in rats. 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.

Protective effects of metformin against aluminum phosphide-induced acute hepato-renal damage in rats: An experimental approach

Phosphine (PH3), from hydrolysis of magnesium, zinc, and aluminum phosphide (AlP), is a rodenticide and insecticide which is used to avoid losses of the agriculture products. However, using of this agent may affect the human health, in a way that poisoning with AlP has a high rate of mortality and morbidities. This study determined the ameliorative effects of metformin (MET) on AlP-induced hepato- and nephro-toxicity in Wistar rats. Male rats were randomly divided into four experimental groups. Group I was the control group received coconut oil by oral gavage, group II was the model group received AlP (12 mg/kg) distributed in coconut oil by oral gavage, group III received MET (200 mg/kg; i.p.), and group IV received MET (200 mg/kg; i.p.) 30 min after intoxication. After 24 h, the serum, liver and kidney tissues were collected for histopathological and biochemical investigations. The levels of kidney function markers, blood urea nitrogen and creatinine, and liver function markers, ALP, AST and ALT, in the plasma were increased significantly followed by AlP intoxication. The results revealed that phosphine causes a significant enhancement of lipid peroxidation, while decreases the activity of superoxide dismutase in both liver and kidney tissues. Furthermore, phosphine significantly induced the up-regulation of TNF-α and phosphorylation of NF-κB in target tissues. Overall, treatment with MET abolished aforementioned alterations resulted by AlP intoxication. Furthermore, histological evaluation indicated a deleterious effect of AlP on the liver and kidney tissues along with marked increase in kidney and liver injury scores, which is mitigated by MET administration. According to our results, although metformin could not bring the changes to the level of the control group, it was indicated that this drug might possess a protective effect against AlP-induced hepato and nephrotoxicity by inhibiting inflammatory responses and oxidative stress.

Histopathological study on the protective effect of vitamin C against paracetamol-induced acute hepatic damage in rat.

Paracetamol (PCM) as analgesic drugs makes hepatotoxicity damage. Vitamin C (VC) has been recognized as an antioxidant and has shown protective effects against hepatotoxicity damage caused by paracetamol. The current investigation aims to study the possible protective effects of VC against hepatic damage induced by PCM in rats. Forty male rats were divided into five groups: The primary group as control; receiving distilled water orally, the second group; receiving 500 mg/kg of VC. The third group; receiving 500 mg/kg of PCM. The fourth group (protective group); receiving VC for 7 days, and then PCM for another 7 days, and the last group treated with a combination of VC and PCM for 14 days. The liver tissues after administration of PCM alone showed different changes such as disrupted lobular architecture with degenerating hepatocytes, dilated congested central vein, and mononuclear cellular infiltration. While the protective group preserved the general architecture and lacked evidence of major morphological. Additionally, VC with PCM showed some alterations in the liver architecture. In conclusion, the results of this study demonstrate that VC was effective in reducing the hepatic damage caused by PCM in male albino rats.

Protective effects of Alstonia congensis Methanolic extract against CCl4 induced liver damage in Wistar rats

The hepatoprotective potential, phytochemical properties, and in vivo antioxidant activities of methanol extract of Alstonia congensis stem bark were investigated against carbon tetrachloride (CCl4) induced hepatic damage in Wistar rats. The animals (thirty) were separated randomly into five groups of each six rats and kept under standard state (temperature 25± 2) and fed standard rat pellets and water ad libitum. Liver toxicity in rats was achieved by the intraperitoneal injection of a single dose of 3 ml/kg of CCl4 in olive oil, after oral treatment of rats with 200 and 400 mg/kg of methanol extract of A. congensis or silymarin (50 mg/kg/day) for fourteen days. Then the rats were sacrificed by cervical dislocation and blood samples collected through cardiac puncture, while the liver tissues were removed for the biochemical tests. Hepatotoxic changes were measured by evaluation of some hepatic enzymes, markers of oxidative stress, and histopathological examination. The phytochemical analysis of the extracts displayed the presence of Alkaloids, Saponins, Tannins, Terpenoids, Steroids, Anthocyanin, Flavonoids, Anthraquinones, and Phenols. Treatment of rats with methanol extracts of A. congensis resulted in a significant (p < 0.05) decrease in the values of serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, tissue lipid peroxidation (LPO), as well as an increase (p < 0.05) in the levels of total protein, albumin, reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) to near normal level relative to the CCl4 intoxicated control group (negative control). These observations were buttressed by the histopathological results. Thus, the results revealed that methanol extracts of A. congensis stem bark possess in vivo antioxidant and hepatoprotective effects against CCL4 induced hepatic damage in rats (dose-dependently), which could be attributed to its phytoconstituents.

Evaluation of Polyherbal preparation of Livina against Ethanol Induced Liver Dysfunction

The present study was performed to evaluate the hepatoprotective activity of ployherbal preparation of livina against ethanol-induced hepatotoxicity in rats. Four groups of adult albino wistar rats were taken for the study. Rats were divided into four groups each containing 6 animals. Group first is normal group received the normal saline 10ml/kg for 21th days. Group second negative control this group received ethanol 12ml/kg bw per day is standard dose of this group is Silymarin (100mg/kg) daily for 21th days and in 21th day administered ethanol. Group third is standard dose of this group is Silymarin (100mg/kg) daily for 21th days and in 21th day administered ethanol. Silymarin and ethanol is administered orally. Fourth group is treated with ethanol + livina (Herbal capsule). The level of Serum Glutamic Pyruvic Transaminase Test (SGPT), Serum Glutamic-Oxaloacetic Transaminase Test (SGOT), alkaline phosphatase (ALP) and total bilirubin were determined to assay hepatotoxicity. Ethanol administration caused severe hepatic damage in rats as evidenced by elevated serum SGPT, SGOT, ALP and total bilirubin levels. The polyherbal preparation of livina and silymarin administration prevented the toxic effect of ethanol. The present study concludes polyherbal preparation of livina that has significant hepatoprotective activity against ethanol induced hepatotoxicity, which may be associated with its bioactive component.

Hepatoprotective and Anti-Oxidant Study of Mukta Bhasma (Calx of Cultured Pearls) Against CCl4-Induced Hepatic Damage in Rats (In-Vivo).

Mukta Bhasma (MB) is a traditional Ayurvedic preparation for upper respiratory and lower respiratory conditions, eye disorders, powerful cardiac tonic, immune-regulator, mood elevator and known to promote strength, intellect and semen production. Mukta bhasma is prepared using direct heat as a media of transformation. Mukta Bhasma was evaluated for its hepatoprotective and antioxidant activities against Carbon tetrachloride (CCl4) induced liver damage in wistar albino rats. Mukta Bhasma (100mg/kg, 200mg/kg and 300mg/kg) was administered to experimental rats for 10 days. Silymarin (25mg/kg) was given as the standard drug. The hepatoprotective activity was assessed using various serum biochemical parameters like (SGOT), (SGPT), Total and Direct bilirubin (TB and DB), Alkaline phosphatase (ALP), Total Triglycerides (TG) and Total Cholesterol (TC). Lipid peroxidation (LPO), Reduced Glutathione (GSH) and Catalase (CAT) were determined to explain the antioxidant activity of Mukta Bhasma. The substantially elevated levels of SGOT, SGPT, TB and DB, ALP, TG and TC due to CCl4 treatment were restored towards near normal by Mukta bhasma (MB) of 200mg/kg dose. Administration of MB 200mg has shown significant reduction in the biochemical parameters like SGOT, SGPT, ALP, Bilirubin, Total cholesterol and Total triglycerides with significance of p&lt;0.001 in all the parameters when compared to CCl4 group. Also, they were near to the standard Silymarin group. Mukta bhasma 200mg has shown significant (p&lt;0.001) reduction in the LPO level, increase in CAT and GSH representing significant antioxidant activity of Mukta bhasma. The histopathological study showed reduction in fatty degeneration of liver in MB 200mg/kg body weight. Thus, results revealed that Mukta bhasma afford significant hepatoprotective and antioxidant effects in CCl4 induced hepatic damage.&#x0D;

Antioxidant and hepatoprotective potentials of olive (Olea europaea L. var. Sigoise) leaves against carbon tetrachloride-induced hepatic damage in rats, and investigation of its constituents by high-performance liquid chromatography-mass spectrometry

The present work explored the preventive potential of ethanolic extract of Olea europaea L. (EEOE) leaves against CCl4-induced liver injury in rats. The fingerprint chromatogram of EEOE was determined by HPLC-MS analysis. The antioxidative potential of EEOE was determined by adopting three approved in vitro methods. The EEOE was orally given at a dose of 400 mg/kg, once a day, for 15 days continuously, succeeded by intraperitoneal (i.p.) injection of CCl4 (0.2%). The hepatoprotective potential was evaluated by estimating biochemical parameters including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, total cholesterol, and triglycerides in the bloodstream. In vivo, the antioxidant ability against CCl4-induced liver injury in rats was assessed by estimating the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total reduced glutathione, and lipid peroxidation in the liver tissues. Further, histological analyses were performed to evaluate the degree of hepatic damage. Nine compounds were identified in the EEOE, principally oleuropein, luteolin-7-O-glucoside, and apigenin. The EEOE exhibited strong radical scavenging activity in DPPH assay. The EEOE significantly decreased the augmentation of serum cholesterol, TG, ALT, AST, ALP, and total bilirubin contents. It also restored hepatic SOD, CAT, GSH-Px activities, and glutathione (GSH) amount, and lowered lipid peroxidation amount comparable to the standard silymarin. The biochemical data were complemented with histological conclusions. These findings are indicative of the protective potential of the EEOE against CCl4-induced hepatotoxicity, which is possibly related to the potent antioxidative capacity of its phenolic compounds.

Evaluation of antiobesity and hepatorenal protective activities of Salvia officinalis extracts pre-treatment in high-fat diet-induced obese rats.

The present study evaluated the effects of Hail Salvia officinalis total extract (SOTE) and its high flavonoid fraction (SOHFF) on the high-fat diet (HFD)-induced obesity and hepatorenal damage in rats. Salvia officinalisplants were collected from Hail region, Saudi Arabia. Rats were fed HFD and supplemented orally with SOTE (250mgkg-1) or SOHFF (100mgkg-1) or simvastatin (SVS; 10mgkg-1) every day for 8weeks. Compared to the controls, HFD-induced obesity led to significant increases in body weight, body weight gained, blood insulin, leptin, cardiac enzymes (LDH and CPK) activity, and atherogenic index (AI). HFD rats also showed higher levels of hepatic and renal function biomarkers (ALT, urea, and creatinine), as well as lower levels of PPARγ and Nrf2-gene expression and a disrupted lipid profile. Moreover, HFD rats had lower levels of hepatic and renal antioxidant biomarkers (CAT, GPx, SOD, GR, and GSH), accompanied by higher levels of hepatic and renal lipid peroxidation (LPO), nitric oxide (NO), and inflammatory mediators (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)). In addition, histological examination of hepatic and renal tissues revealed histopathological changes that validated the biochemical findings. Compared to HFD group, SOTE and SOHFF treatment led to marked amelioration of all the aforementioned parameters. Collectively, supplementation with SOTE and SOHFF effectively reversed HFD-induced alterations through its antioxidant, hypolipidemic, and anti-inflammatory properties. Hence, SOTE and SOHFF have therapeutic potential in controlling obesity and related pathologies.

Ornipural® Mitigates Malathion-Induced Hepato-Renal Damage in Rats via Amelioration of Oxidative Stress Biomarkers, Restoration of Antioxidant Activity, and Attenuation of Inflammatory Response.

The current study was instigated by investigating the ameliorative potential of Ornipural® solution against the hepato-renal toxicity of malathion. A total number of 35 male Wistar albino rats were divided equally into five groups. Group 1 served as control and received normal saline intraperitoneally. Group 2, the sham group, were administered only corn oil (vehicle of malathion) orally. Group 3 was orally intoxicated by malathion in corn oil at a dose of 135 mg/kg BW via intra-gastric gavage. Group 4 received malathion orally concomitantly with Ornipural® intraperitoneally. Group 5 was given Ornipural® solution in saline via intraperitoneal injection at a dose of (1 mL/kg BW). Animals received the treatment regime for 30 days. Histopathological examination revealed the harmful effect of malathion on hepatic and renal tissue. The results showed that malathion induced a significant decrease in body weight and marked elevation in the activity of liver enzymes, LDH, and ACP. In contrast, the activity of AchE and Paraoxonase was markedly decreased. Moreover, there was a significant increase in the serum content of bilirubin, cholesterol, and kidney injury markers. A significant elevation in malondialdehyde, nitric oxide (nitrite), and 8-hydroxy-2-deoxyguanosine was observed, along with a substantial reduction in antioxidant activity. Furthermore, malathion increased tumor necrosis factor-alpha, the upregulation of IL-1B, BAX, and IFN-β genes, and the downregulation of Nrf2, Bcl2, and HO-1 genes. Concurrent administration of Ornipural® with malathion attenuated the detrimental impact of malathion through ameliorating metabolic biomarkers, restoring antioxidant activity, reducing the inflammatory response, and improving pathologic microscopic alterations. It could be concluded that Ornipural® solution demonstrates hepatorenal defensive impacts against malathion toxicity at biochemical, antioxidants, molecular, and cellular levels.

Protective and antioxidant activities of vitamin E in carbofuran-induced hepatic damage in rats

Protective and antioxidant activities of vitamin E in carbofuran-induced hepatic damage in rats

Thymol Reduces Hepatorenal Oxidative Stress, Inflammation and Caspase-3#xd; Activation in Rats Exposed to Indomethacin

ABSTRACT Indomethacin (IND) is a non-steroidal anti-inflammatory drug with many pharmacological benefits and multi-organ toxicities. Thymol (THY) is a natural phenolic monoterpenoid with many biological properties. However, there is scarcity of information on its potential on IND-induced hepatorenal damage in rats. This study investigated the effect of THY on IND-induced hepatorenal damage in rats. The four experimental groups contain control, IND alone (5 mg/kg), THY alone (250 mg/kg) and co-treated group that were treated orally for 21 consecutive days. Twenty four hour after treatments, rats were sacrificed and markers of hepatorenal damage (ALT, ALP, AST, G6PDH, GGT, BIL, CHOL, GLDH, LDH, MDH, SDH, creatinine, urea, uric acid, cystatin-C and electrolytes), antioxidant status markers, myeloperoxidase (MPO) activity, nitric oxide (NO), lipid peroxidation (LPO), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) levels and caspase-3 activity were evaluated. IND increased hepatorenal toxicity, inflammatory and apoptotic markers and decreased antioxidant status. Co-administration of IND with THY significantly decreased hepatorenal damage biomarkers improved the antioxidant status and reduced the MPO activity, LPO, NO, TNF-α, IL-1β levels and caspase-3 activity in the liver and kidney of rats. In conclusion, THY mitigates against IND-induced oxidative stress, inflammation and caspase-3 activation in the liver and kidney of the rats.

Synergistic hepatoprotective effects of ω-3 and ω-6 fatty acids from Indian flax and sesame seed oils against CCl4-induced oxidative stress-mediated liver damage in rats

Flaxseed (FS) and sesame seed (SS) are traditional and functional foods in traditional Indian medicine for treating various disorders. The present study investigated the hepatoprotective effects of bioactive-fatty acids (FAs) from FS and SS against carbon tetrachloride (CCl4)-induced hepatic damage in rats. Pre and post-treatments for 28 consecutive days significantly increased the activities of in vivo antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and peroxidase (POX), whereas, lipid peroxidation (LPO) activity was markedly decreased in a dose-dependent manner in liver and kidneys. A significant reduction was observed in the hematological parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin in the serum of post-treated animals compared to the negative control. The results were confirmed histopathologically. The results suggested that the ω-3 and ω-6 FAs from flaxseed oil (FSO) and sesame seed oil (SSO), respectively, showed potential synergistic hepatoprotective and antioxidant effects that were mediated mainly by ω-3 and ω-6 FAs present in the respective seed oils.

Influence of hydroethanolic extract of Cassia spectabilis leaves on diclofenac-induced oxidative stress and hepatorenal damage in Wistar rats

BackgroundThe medicinal potential of plant extracts for the management of liver and kidney disorders in humans has been harnessed for the past several centuries. However, the abundant plant resources have not been fully investigated, thus this study was initiated to evaluate the influence of Cassia spectabilis leaves extract (CSE) on diclofenac-induced oxidative stress and hepatorenal damage in Wistar rats. The rats in the 1st group were injected with normal saline, and rats in the 2nd group were injected with diclofenac sodium (DF) by intramuscular route. Rats in the 3rd to 5th groups were treated with graded doses of CSE by oral gavages, and injected with DF. The serum markers of oxidative stress and hepatorenal damage in rats were estimated by biochemical assays. In addition, histological examinations of liver and kidney tissues were evaluated.ResultsThere was significant (p < 0.05) increase in the levels of total bilirubin, ALT, AST, ALP, GGT, LDH, urea, creatinine, uric acid, potassium ions, and MDA of rats injected with DF when compared with normal control. The treatment of DF-injected rats with CSE significantly (p < 0.05) reduced the levels of these markers of hepatorenal damage in rats when compared with DF control. There was significant (p < 0.05) decrease in the levels of GSH, SOD, CAT, GPx, GST, sodium ions, proteins and G6Pase after injection of rats with DF when compared with normal control. However, treatment of DF-injected rats with CSE significantly (p < 0.05) increased the levels of these markers of antioxidant status and oxidative damage in hepatorenal tissues of rats when compared with DF control. The photomicrographs of hepatorenal tissues showed structural features which corroborated our biochemical findings in this study.ConclusionThe findings of this study have shown that CSE may have protective effect against DF-induced oxidative stress and hepatorenal damage in Wistar rats. Thus, the medicinal potential of this plant leaves extract may be harnessed for the development of phytotherapeutic products.

Ficus glumosa Del. reduces phenylhydrazine-induced hemolytic anaemia and hepatic damage in Wistar rats.

Anemia is a direct or indirect consequence of oxidative stress via free radicals on erythrocytes and subsequently on other tissues like liver. Ficus glumosa constitute a rich pharmacologically compound that can prevent or repair oxidative damage. Therefore, this study seeks to evaluate the effect of F.glumosa on phenylhydrazine-induced hemolytic anemia and hepatic damage in rats. Twenty-four (24) albino Wistar rats were assigned to four (4) experimental groups (n=6) as follows: Group I (non-anemic control) and Group 2 (anemic control) received normal saline, while Group III and IV (test groups) 200 and 400mg/kg of aqueous leaf extract of F.glumosa (ALEFG), respectively. All the groups were treated orally (via a cannula) for seven consecutive days. Intraperitoneal (IP) injection of phenylhydrazine (PHZ) at 40mg/kg for two consecutive days induced hemolytic anemia in group II to IV before treatment. Rats of all groups were anaesthetized and sacrificed 24h after the last treatment. Blood and liver samples were collected for some hematological indices, liver function test, antioxidant parameter and histological analysis. The LD50 of ALEFG was assessed orally in rats and found to be above 5,000mg/kg body weight. Significant (p<0.05) decreases in the level of red blood cell (RBC), hemoglobin (HGB) concentrations and packed cell volume (PCV) by 50% after 2days of PHZ induction, were attenuated by more than 50% after 7days administration of ALEFG at 200 and 400mg/kg. The percentage change in body weight increased significantly (p<0.05) after 7days post PHZ-induced anemia, but those that received oral administration of ALEFG (at 200 and 400mg/kg) for 7days increased significantly (p<0.05) by more than 2%, dose-dependently compared to anemic untreated group. Increased level of serum ALT, AST, ALP and GGT in PHZ-induced anemic animals, were significantly (p<0.05) attenuated in the groups that received oral administration of ALEFG (at 200 and 400mg/kg) for 7days. Decreased level of catalase (CAT) and superoxide dismutase (SOD) activities with concomitant increase in malondialdehyde (MDA) content from PHZ-induced untreated group, were significantly (p<0.05) mitigated in the rats that received oral administration of ALEFG (at 200 and 400mg/kg) for 7days. Histopathological analysis showed that ALEFG could remarkably though not completely mitigated PHZ-induced hepatic damage. Our data suggests that the leaves of F.glumosa contain important antioxidant(s) that could effectively reduce hemolytic anemia and hepatic damage, especially during phenylhydrazine-induced toxicity.

Isoliquiritigenin prevents Doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1

This study evaluated if the hepatic protective effect of Isoliquiritigenin (ISL) against doxorubicin (DOX)-treated rats involves upregulating sirtuin-1 (SIRT1) signaling. Adult male was divides into 5 groups (n = 6 rats/each) as control (vehicle), ISL (25 mg/kg), DOX (15 mg/kg), DOX + ISL, and DOX + ISL + EX-527 (a SIRT1 inhibitor, 5 mg/kg). ISL and EX-527 were administered 10 days before and after the single treatment of DOX. Also, cultured AML-12 hepatocytes (5 ×104) were treated with 10 µM of ISL for 24 h with or without DOX-treatments (10 µM) and in the presence or absence of EX-527 (5 µM). ISL prevented hepatocyte damage and decreased serum levels of hepatic transaminases, hepatic levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic mRNA levels of Bax and caspases-3,8, and 9. In the liver of the control and DOX-treated rats, ISL reduced levels of malondialdehyde (MDA) but increased hepatic levels of glutathione (GSH), superoxide dismutase (SOD), and catalase, as well as mRNA levels of Bcl2. In vitro, ISL stimulated cell survival and lowered levels of ROS but increased GSH levels. In vivo and in vitro, in the livers of control and DOX-treated animals, ISL significantly increased the nuclear activity and mRNA levels of SIRT1, enhanced the nuclear levels of Nrf2, and reduced nuclear levels of NF-κB p65. In conclusion, ISL alleviates DOX-induced hepatocyte toxicity by stimulating the Nrf2/antioxidants axis and concomitant suppression of NF-κB, mainly by upregulating/activating SIRT1.

Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets.

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action. Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl4 induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results. Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl4-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGFβR1, COL3A1, and TGFβR2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs. Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects.