Relative Liver Weight Research Articles

Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study

Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. Hence cost-effective drugs with fewer side effects as a standard supportive therapy might yield substantial advantages in efficacy and safety. Kadukkai maathirai (KM) is being used as a supplement in hepatocellular carcinoma. We evaluated whether KM has any preventive action on cancer progression in diethyl nitrosamine (DEN) - induced HCC in rats. Methods DEN was injected to produce HCC in rats, which was confirmed after 16 weeks. All the rats were orally administered KM for 4 weeks. Hepatoprotective potential (serum AST, ALT, ALP, Bilirubin) and anticancer efficacy (body weight, nodule count, tumor progression by histopathology, expression of GSTM1 by Liquid chromatography-mass spectrometry (LC-MS), and In-silico analysis of phytoconstituents against β catenin and LRP analysis were evaluated. Results KM prevented cancer progression against DEN-induced HCC by an increase in GSTM1, a phase II detoxifying enzyme. It significantly reversed altered nodule count, relative liver weight, body weight, and histopathological features of HCC. In silico analysis of phytoconstituents of KM showed that they modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin. Conclusions Our results elucidate the potential of KM as a supplement in HCC by reducing nodule count, protecting the liver from further damage, GSTM1 expression, and inhibiting armadillo repeat region of β catenin.

Ameliorative Effects of Phyto-estrogen ‘Genistein’, Homeopathic Combination ‘R-85’and Captopril on Body Weight, Organ Weight, Feed and Water Intake in L-NAME Induced Hypertensive Wistar Rats

Hypertension is associated with the development and progression of severe damage to organs. Meager studied has been found on the effect of Phyto-estrogen ‘genistein’ and homeopathic combination ‘R-85’ as antihypertensive action which may aid in main therapy of hypertension. Thus, present study aims to evaluate the effect of ‘genistein’, ‘R-85’ and ‘captopril’ on body weight, organ weight feed and water intake in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertensive male wistar rats. After acclimatization, the male wistar rats were divided into 5 groups of 5 rats in each group. The rats except control group (group-I) were treated with L-NAME (@50mg/kg, in drinking water, group-II), L-NAME + Genistein (@50mg/kg, per os, group-III), L-NAME + R-85 (@ 5 drops, twice daily, group-IV) and L-NAME + Captopril (@50 mg/kg, per os, group-V) daily for 42 days. The study was conducted for a period of 42 days. During the experimental period, weight of rats, feed intake and water intake was measured weekly. At the end of the experimental period, rats were sacrificed andheart, kidneys and liver were weighed. After treatment with genistein, R-85 and captopril an increase in body weight was found as compared to L-NAME group. On similar treatment there was an increase in feed intake per 100 g of rat was found compared to L-NAME hypertensive group per week. Unlike feed intake, treatments decrease the water intake per 100 g of rat compared to L-NAME group per week. A significant increase in the relative weights of the liver and kidney was found in L-NAME group compared to control. Whereas, treatment with R-85 and captopril significantly decreased the relative weight of liver and kidney as compared to L-NAME group. Thus finding of the present study discloses ameliorative effect of genistein, R-85 and captopril on hypertensive rats.

In vitro and in vivo evaluation of the nutritional value of various hydrolyzed feather meals and comparison of their effect on performance and carcass characteristics of broilers

In the current study, the nutritional value of various hydrolyzed feather meals (HFM) was investigated in two separate experiments (an in vitro and an in vivo experiment). The in vitro experiment was based on a completely randomized design with five replications and seven treatments including (1) Raw feather meal (RFM), (2) HFM by autoclave (Au-HFM), (3) Fermented feather meal (FFM) by Bacillus licheniformis (Bl-FFM), (4) FFM by Bacillus subtilis (Bs-FFM), (5) FFM by Aspergillus niger (An-FFM), (6) FFM by Bacillus licheniformis + Bacillus subtilis + Aspergillus niger (Co-FFM), and (7) HFM by an enzyme (En-HFM). The highest in vitro pepsin-pancreatin and apparent ileal CP digestibility were observed in Co-FFM, and the lowest amount belonged to RFM (P < 0.05). For the in-vivo experiment, 480 1-d-old male Ross 308 broilers were distributed in the experimental units in a completely randomized design with 8 treatments and 5 replicates (12 chicks/replicate). The treatments were: (1) Control diet (without feather meal (FM)), (2), (3), (4), (5), (6), (7), and (8), diets containing 4 % RFM, Au-HFM, Bl-FFM, Bs-FFM, An-FFM, Co-FFM, and En-HFM, respectively. For the in-vivo study, the birds fed control and Co-FFM diets had the highest feed intake, body weight gain, and the lowest feed conversion ratio compared to the other treatments (P < 0.05). The broilers fed the control and FFMs diets had the lowest relative weight of abdominal fat and liver compared to the other groups (P < 0.05). Therefore, our findings advise the poultry feed industry to look for Co-FFM as an effective alternative and cheaper feed ingredient to replace part of soybean meal in poultry diet.

Toxicological profile of Balanites agyptiaca in albino Wistar rats

Background: Balanites aegyptiaca (BAE) is a thorny tree that grows in most arid and semi-arid areas of Africa, the Middle East and India. It is used in traditional medicine for its cardioprotective, deworming, antihelmintic, anti-infectious and antifungal properties. Excessive consumption of this plant's products can present risks of intoxication for consumers. Objective: The aim of this study was to assess the acute and subchronic oral toxicity of the aqueous extract of Balanites aegyptiaca leaves and roots, with a view to ensuring the safety of consumers of this plant. Method: Acute toxicity was carried out in accordance with the OECD experimental protocol. The plant extract tested was administered orally to female rats at a single dose of 2000 mg/kg. These animals were observed for 14 days. For the subchronic toxicity study, the aqueous extract was administered daily orally to male and female rats at different doses (250, 500 and 1000 mg/kg) for 30 days. After the treatment period, the animals were sacrificed for hematological, biochemical and histopathological analyses. Results: The results of the acute oral toxicity test showed that the aqueous extract of Balanites aegyptiaca leaves and roots was non-toxic at a dose of 2000 mg/kg. During the sub-chronic test period, observation of rat signs and behaviour revealed no abnormalities in the groups of animals treated with the extract compared with controls. A significant variation in relative heart and liver weights was observed at 1000 mg/kg. In addition, there was a significant reduction in concentrations of aspartate aminotransferase, total cholesterol, triglycerides and low-density lipoproteins in these rats. Compared with control groups. There was also a significant decrease in hemoglobin and mean corpuscular hemoglobin, with an increase in lymphocytes and white blood cells at the same dose of 1000mg/kg. Histological examinations of the kidneys and liver showed normal renal architecture, and the liver also showed normal hepatic architecture with slight degeneration at a dose of 1000mg/kg of the extract tested. Conclusion: Single administration of the 2000 mg/kg dose did not induce signs of significant toxicity in rats. However, in long-term oral treatment, safety measures must be taken. Thus, sub-chronic oral exposure of BAE to lower doses is recommended, while higher doses, of the order of 1000 mg/kg, should be avoided.

Oxidative stress causes liver injury via the damage of redox system and the apoptosis induced by mitochondria of broiler

The aim of this study was conducted to explore the effects of oxidative stress on the redox system, mitochondrial function, and apoptosis in liver of broilers. 144 one-day-old male Ross-308 broilers from the same batch had been prepared in advance and were divided into 3 treatments: normal control group (without intraperitoneal injection), normal saline group (intraperitoneal injection of normal saline), and hydrogen peroxide (H2O2) group (intraperitoneal injection of H2O2) with 6 replicates of 8 chickens each. The experimental period was 42 days. The injection volumes were 1.0 mL/kg of Ross-308 broiler body weight. On the 42nd day of the experimental period, two Ross-308 broilers were randomly selected from each cage, a total of 36 broilers were stunned by electric shock and slaughtered to collect liver samples. The results showed that compared with the non-injection group and the injection of saline group, H2O2 exposure elevated the relative weight of liver and the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum of Ross-308 broilers (p < 0.05). Meanwhile, compared with the non-injection group and the injection of saline group, the H2O2 exposure increased the levels of reactive oxygen species (ROS), MDA, lipid peroxide (LPO) and protein carbonyl, decreased the activities of total superoxide dismutase (T-SOD), catalase (CAT), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) (p < 0.05). Compared with the non-injection group and the injection of saline group, the H2O2 exposure caused microvesicular steatosis and mitochondrial vacuolisation in the liver tissues of broilers. Additionally, after H2O2 exposure, the levels of nuclear factor erythroid 2–related factor 2 (Nrf2) positive cells were reduced and the relative percentage of hepatocyte apoptosis were increased in the liver tissues of broilers (p < 0.05). The conclusion of this study is that the oxidative stress induced by intraperitoneal injection of H2O2 could induce excessive production of ROS in broiler liver, which damage the antioxidant status and mitochondrial function of liver cells, leading to cell apoptosis. HIGHLIGHTS Oxidative stress can cause severe damage to the liver of broilers. Oxidative stress can mainly damage liver antioxidant function Oxidative stress can induce cell apoptosis by damaging mitochondria in the liver of broilers

Exploring the hepatoprotective potential of the probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide-postbiotic on ibuprofen-induced acute liver injury in rats.

The present study investigates the hepatoprotective effect of a probiotic Lactiplantibacillus plantarum E1K2R2 and its exopolysaccharide (EPS) against ibuprofen-induced acute liver injury, and to explore the involved underlying mechanisms. Hepatotoxicity was induced by administration of a single dose of ibuprofen (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU) and its EPS (200 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. Liver toxicity was assessed by monitoring levels of serum liver enzymes, liver relative weight, oxidative stress and inflammatory markers, and through histopathological analysis. The results showed that ibuprofen administration significantly increased (P < 0.05) liver relative weight, elevated levels of alanine-amino transferase (ALT), aspartate-amino transferase (AST), decreased hepatic gluthatione (GSH) and endogenous antioxidant enzymes including, superoxide dismutase (SOD), catalase (CAT) and increased malondialdehyde (MDA) levels, nitric oxide (NO) and myeloperoxidase (MPO) in hepatic tissues. However, pre-treatment with Lpb. plantarum E1K2R2 and its EPS significantly attenuated these toxicity manifestations. Both pre-treatments restored liver weight, normalized transaminase enzyme levels, enhanced the activity of liver antioxidant enzymes (SOD and CAT), increased GSH content, and significantly reduced NO, MPO and MDA levels (P < 0.05), indicating their protective role against oxidative stress and inflammatory response induced by ibuprofen. Furthermore, histopathological analysis confirmed regular liver morphology in rats pre-treated with the probiotic and its EPS. These findings highlight the potential effectiveness of the probiotic Lpb. plantarum E1K2R2 and its EPS in mitigating ibuprofen-induced liver toxicity.

Protective potential of Bacillus subtilis (NMCC-path-14) against extraarticular manifestations during acute and sub-acute phase of arthritis using mice model

Extra-articular manifestations (EAM), which are associated with rheumatoid arthritis (RA), affect the quality of life of patients and are one of the critical causes of early mortality. This study was aimed at investigating whether Bacillus subtilis NMCC-path-14 (1 × 108 CFU/animal/day) could serve as a valuable therapeutic agent in managing EAM using complete Freund's adjuvant (CFA) induced arthritis during acute and sub-acute phases. Arthritis was induced using intra-dermal administration of CFA in the right hind paw of mice on day 1. Dexamethasone (Dexa) (5 mg/kg/day/animal) was used as a standard treatment. Animals in Dexa and Bacillus subtilis concurrent treatment (BS-CT) received treatments on day 1. The Bacillus subtilis pre-treatment (BS-PT) group received a probiotic dose 7 days before arthritis induction. Parameters like body weight, relative organ weight, colon length, hematology, serum biochemistry, antioxidant capacity, and histopathology of liver, kidney, spleen, colon, stress-related behavioral changes, and cortisol levels were evaluated on days 7 (acute) and 14 (sub-acute). Dexa failed to manage the EAM in arthritic mice and instead exacerbated them. On the other hand, B. subtilis NMCC-path-14 significantly declined EAM with no notable side effects, highlighting its safety and effectiveness. The current data show that B. subtilis NMCC-path-14 may be an alternative option for arthritis treatment that can reduce systemic symptoms associated with arthritis. More studies are required to comprehend the underlying mechanisms of mitigating the EAM by B. subtilis NMCC-path-14.

Thymol, a Dietary Monoterpene, Abrogates Hexachlorobenzene-Induced Hepatic Dysfunction Via Different Mechanisms

Thymol (2-isopropyl-5-methyl-phenol) is a natural monoterpene phenolic antioxidant that has anti-inflammatory and anti-apoptotic potentials in experimental studies. Literatures are scarce on effects of hexachlorobenzene-induced hepatic damage. Therefore, this study investigated the ameliorating potential of thymol (THY) on hexachlorobenzene (HCB)-induced hepatic damage as well as the effects on the antioxidant status, polyamine catabolism, inflammatory and apoptotic processes. Thirty-two adult male rats were daily treated orally by gavage for 25 days and allocated into four groups; control group received corn oil, HCB alone group (15 mg/kg b.wt), THY-treated group (100 mg/kg b.wt) and HCB + THY-treated group. The results showed that HCB significantly reduced the body weight with concurrent increase in relative liver weight accompanied by widespread histological aberrations. Furthermore, HCB-treated rats revealed increases in hepatic putrescine oxidase, spermine oxidase, and myeloperoxidase activities, tumor necrosis-α and interleukin-1β levels, caspase-3 activity, induced oxidative damage as evidenced by elevated malondialdehyde (MDA) levels and significant reduction in antioxidant enzyme activities and reduced glutathione (GSH). However, co-administration of THY with HBC abated the hepatic damage by preventing the generation and release of reactive oxygen species, improving the antioxidant system, down-regulated polyamine catabolism, inflammatory and apoptotic responses. The findings of this study revealed that HCB acts as a hepatotoxicant and thymol might be a possible future therapeutic agent for HCB-induced hepatic damage.

Effects of protein grass hay as alternative feed resource on lamb's fattening performance and meat quality

Protein grass hay (PGH) was used as a new feed source for lambs to study its effect on fattening performance and meat quality. Fifty-six male lambs were allotted to four experimental groups and fed for eight weeks either alfalfa hay (AH)-based diet (control) or diets in which AH was replaced with 33 %, 66 %, or 99 % PGH. The inclusion of PGH did not affect final body weight, dry matter intake, average daily gain, feed conversion ratio, or carcass weight. Moreover, substituting AH with PGH at any level did not influence the ruminal fermentation or serum biochemical parameters, meat color, water holding capacity, shear force, or amino acid profile. However, relative liver weight was increased with 66 % substitutions. Furthermore, replacing 99 % AH with PGH decreased the meat's pH at 24 h. Higher levels of C18:3n-3, C20:5n-3, and total n-3 PUFA and a lower ratio of n-6: n-3 PUFA were also observed in meat from lambs fed PGH at 99 %. These findings suggest that PGH could be incorporated into the lamb's diet up to 99 % without compromising fattening performance and body health while improving their meat n-3 PUFA deposition.

Effectiveness of Hydrated Sodium Calcium Aluminosilicates and Discarded Date Pits as Dietary Adsorbents for Aflatoxin B1 in Enhancing Broiler Chicken Productive Performance, Hepatic Function, and Intestinal Health.

The research aimed to evaluate how effective hydrated sodium calcium aluminosilicates (HSCASs) and discarded date pits (DDPs) are as dietary adsorbents for aflatoxin B1 (AFB1) in enhancing the performance and health of broiler chickens aged 16 to 30 days. A total of 240 Ross 308 straight-run broilers were randomly allocated into four dietary groups, each with 10 replicates: a control diet, a control diet with 1000 ppb AFB1, an AFB1-contaminated diet with 0.5% HSCAS, and an AFB1-contaminated diet with 4% DDP. Incorporating HSCASs or DDPs into the AFB1-contaminated diet resulted in significant improvements across various parameters, involving increased body weight, improved feed conversion ratio, higher dressing percentage, decreased relative weights of kidney and spleen, elevated serum levels of total protein, globulin, and glucose, reduced serum alanine aminotransferase activity, and heightened hepatic protein concentration and glutathione peroxidase activity, along with diminished hepatic malondialdehyde content and glutamic oxaloacetic transaminase activity. Moreover, both supplements led to increased ileal villus height and surface area, enhanced apparent nitrogen-corrected metabolizable energy digestibility, and decreased AFB1 residues in the liver and kidney. Moreover, the dietary inclusion of DDPs significantly decreased relative liver weight, raised serum albumin concentration, lowered serum alkaline phosphatase activity, enhanced hepatic total antioxidant capacity level, and augmented ileal villus width. Conversely, the dietary addition of HSCASs significantly heightened apparent crude protein digestibility. In conclusion, the inclusion of HSCASs and DDPs in AFB1-contaminated diets can mitigate the toxic effects of AFB1 on broiler chickens, with DDPs exhibiting additional advantages in optimizing liver function and gut morphology.

Effect of Ruta chalepensis Oil Extract against Hepatotoxicity of Potassium Bromate on Liver Weight and Some Biochemical Parameters of Male Rats

Potassium bromate (KBrO3) is widely used as improving additive for bread making. Ruta chalepensis (R. chalepensis) is used throughout the world as a herbal remedy for various illnesses. The present study aimed to investigate the possible protective and curative effects of R. chalepensis oil extract against KBrO3 toxicity on male rats. Fifty male albino rats divided into five groups. Group (1): served as a control group. Group (2): administered R. chalepensis. Group (3): received KBrO3. Group (4): protective group. Group (5): therapeutic group. After 2nd and 4th weeks, the determination of liver weights and relative liver weight were calculated, also, the resultant sera were collected for biochemical assays including ASAT, ALP, total proteins, albumin in the blood serum. The results of the present study showed after 4 weeks decrease in liver weight in R. chalepensis, KBrO3 and protective groups. In relative liver weight no changes in all groups except decease in R. chalepensis group. In serum ASAT levels, no changes in all groups except decrease in therapeutic group. Serum ALP levels increased in therapeutic group and highly significantly increased in KBrO3 group. There were increases in total protein levels in all groups. Albumin levels, increased in KBrO3 group and highly increased in protective and therapeutic groups. In conclusion, the administration of R. chalepensis oil extract against KBrO3 toxicity was not beneficial as protective and curative effects in adult male rats.

Early stage Fasciola hepatica infection in growing cattle: impact on weight gain and liver weight determined in flukicide efficacy studies.

Although the negative impact of liver fluke (Fasciola hepatica) infection on production and health in cattle is generally accepted, results of individual research have been variable, ranging from important negative impacts on the animal to minimal or no impact. To add information on the impact of F. hepatica infection in growing cattle, weight gain and liver weight of young experimentally infected animals from seven controlled efficacy studies were analyzed. In each study, fluke naïve animals were inoculated with approximately 450 to 500 F. hepatica encysted metacercariae, blocked on body weight and randomly assigned into one untreated group (controls) and groups which were administered an experimental flukicide when the flukes were 4 weeks old (migrating) and sacrificed 8 weeks thereafter (12 weeks after inoculation). Data of groups which demonstrated >90% reduction of fluke counts following treatment and groups left untreated (total 103 and 47 animals, respectively) were compared. There was a significant (p < 0.0001) negative association between fluke count and weight gain while fluke count and liver weight and fluke count and relative liver weight were positively associated (p < 0.0001). Over the 8-week post-treatment period, flukicide-treated cattle had almost 15% more weight gain than the controls (50.9 kg vs. 44.4 kg; p = 0.0003). Absolute and relative liver weight was significantly (p < 0.0001) lower in flukicide-treated compared to untreated cattle. Overall, this analysis provided evidence of a substantial negative effect of early (migrating) liver fluke infection on the growth of young cattle, likely due to pathology of the liver and associated reduction in its function as the central organ for bioenergy and protein metabolism.

Functional oil in the feeding of heat-stressed Japanese quail

The objective of the present study was to evaluate a blend of functional oils (FO) composed of copaiba and garlic essential oils, pepper oleoresin and cashew nut liquid to mitigate the effects of heat stress on productivity, egg quality, organ morphology of the gastrointestinal tract, serum biochemical profile, nutrient metabolism and body temperature of Japanese quail. A completely randomized design was used in a 3 × 2 factorial scheme (without additive; 300 and 500 mg FO/kg of feed x birds raised in a thermal comfort (TC) and heat stress (HS) environment), with 6 replicates of 8 birds per plot. The birds under HS had lower feed intake (P = 0.0000), egg mass (P = 0.0000), laying rate (P = 0.0000) and higher percentage of infertile non-commercial eggs (P = 0.0004), lower head temperature amplitude (P = 0.0000) and higher average of body temperature (P = 0.0312). HS worsened the external and internal quality of the eggs. Birds kept in HS showed higher values of cholesterol (P = 0.0000) and glutamic-pyruvic transaminase (P = 0.0272). The use of 300 and 500 g FO/ton of feed improved the feed conversion (P = 0.0000) and egg mass (P = 0.0000) of the quail bred under HS, respectively, by 8.4 and 7.2% and increased the relative weight of liver (P = 0.0064) and pancreas (P = 0.0492). The use of such additives also provided a higher % of yolk (P = 0.0018) and reduced the percentage of albumen (P = 0.0029) of the eggs produced in TC, in addition to reducing the amplitude of head temperature (P = 0.0484) of birds bred under HS. The breeding of Japanese quail under HS results in negative impacts on the production, physiological and qualitative aspects of the eggs. The use of 300 g/ton of FO in the diet of Japanese quail leads to improvements in feed conversion, increased liver capacity in nutritional metabolism and results in eggs with a higher proportion of yolks, being, therefore, an alternative for feeding quail in a hot climate.

Toxicological evaluation of Alpinia oxyphylla-derived molecule (PD-00105): In vitro genotoxicity studies and 90-day oral toxicity study in rats

PD-00105 corresponds to a compound initially identified in the fruit of Alpinia oxyphylla Miq., obtained by chemical synthesis and proposed to be use in dietary supplements for its potential neuroprotective properties. The aim of this study was to perform a toxicological evaluation of PD-00105 in accordance with the testing strategy recommended by food regulatory authorities. All studies were conducted in accordance with Good Laboratory Practice (GLP), and followed the Organization for Economic Co-operation and Development (OECD) test guidelines for chemicals. Studies included a bacterial reverse mutation test, one in vitro micronucleus test in mammalian cells, and a repeated dose 90-day oral toxicity study. No sign of toxicity was observed in the two genotoxicity tests. The test item induced a significant liver and kidney toxicity at high doses (50 and 100 mg/kg BW/day), highlighted by significant increases in liver and kidney absolute and relative weights, associated with histopathological findings and concomitant changes in hematology and clinical chemistry. Increases in alanine aminotransferase, alkaline phosphatase, total protein, albumin, globulin, cholesterol, LDL, and HDL have been measured in these two groups. However, findings observed in the low-dose group (10 mg/kg BW/day) were considered as minimal and non-adverse, and were limited to an increase in liver weight in males and in kidneys weight in females, without concomitant changes in blood chemistry. The No Observed Adverse Effect Level (NOAEL) of PD-00105 was established as 10 mg/kg BW/day under the conditions of this study. This study substantiates the use of PD-00105 in dietary supplements at doses of 10 mg/day, taking into account a safety margin factor for dose conversion to humans.

In vivo evaluation of efficacy and safety of Coagulansin-A in treating arthritis

The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model.

Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study

Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. Hence cost-effective drugs with fewer side effects as a standard supportive therapy might yield substantial advantages in efficacy and safety. Kadukkai maathirai (KM) is being used as a supplement in hepatocellular carcinoma. We evaluated whether KM has any preventive action on cancer progression in diethyl nitrosamine (DEN) - induced HCC in rats. Methods DEN was injected to produce HCC in rats, which was confirmed after 16 weeks. All the rats were orally administered KM for 4 weeks. Hepatoprotective potential (serum AST, ALT, ALP, Bilirubin) and anticancer efficacy (body weight, nodule count, tumor progression by histopathology, expression of GSTM1 by Liquid chromatography-mass spectrometry (LC-MS), and In-silico analysis of phytoconstituents against β catenin and LRP analysis were evaluated. Results KM prevented cancer progression against DEN-induced HCC by an increase in GSTM1, a phase II detoxifying enzyme. It significantly reversed altered nodule count, relative liver weight, body weight, and histopathological features of HCC. In silico analysis of phytoconstituents of KM showed that they modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin. Conclusions Our results elucidate the potential of KM as a supplement in HCC by reducing nodule count, protecting the liver from further damage, GSTM1 expression, and inhibiting armadillo repeat region of β catenin.

Olsalazine pretreatment augments chemosensitivity of gemcitabine in hepatocellular carcinoma.

Recently, olsalazine a DNA hypomethylating agent was found to inhibit the growth of breast cancer cells. The present study was carried out to evaluate the effects of olsalazine pretreatment in the potentiation of chemosensitivity of gemcitabine for the treatment of hepatocellular carcinoma (HCC).In silico molecular docking was performed to analyze the interaction of olsalazine and gemcitabine with DNMT1 and DNA, respectively, using the AutoDock tools 1.5.6. Cytotoxicity of olsalazine, gemcitabine, and combination were measured on human HePG2 cells using MTT assay. Antiproliferative effects were assessed using animal model of N-nitrosodiethylamine and carbon tetrachloride-induced HCC. Treatment was initiated from 8th week of induction to 11th week and change in body weight, liver weight, and survival rate were measured. Following treatment, blood samples were collected for estimation serum biochemistry. Blood serum was used for the estimation of inflammatory cytokines tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6), C-reactive protein[CRP],lactate dehydrogenase (LDH), and P53 levels. Oxidative stress markers were measured in liver tissue homogenates. Histopathology and immunohistochemistry (IHC) were performed on liver sections to detect the morphological changes and P53 expression. Docking analysis revealed the interactions between olsalazine and DNMT1 with a binding energy score of -5.34 and gemcitabine and DNA with a binding energy score of -5.93. Olsalazine pretreatment potentiated the antiproliferative effect of gemcitabine in cell line study. In the group receiving olsalazine pretreatment showed significant reductions in relative liver weight and improved survival rate of gemcitabine treatment group. Serum biochemical markers:serum glutamate pyruvate transaminase,serum glutamic oxaloacetic transaminase, alkaline phosphatase, and bilirubin revealed improved liver functions. Olsalazine pretreatment also reduced the levels of inflammatory markers like CRP, LDH, TNF-α, and IL-6 and oxidative stress markers dose dependently. Histopathology and IHC showed improved liver morphology with potentiated the induction of P53 upon olsalazine pretreatment in combination with gemcitabine. In conclusion, sequential combination of olsalazine and gemcitabine improvedthe treatment outcomes during the progression of HCC.

Mode of action analysis for fluxapyroxad-induced rat liver tumour formation: evidence for activation of the constitutive androstane receptor and assessment of human relevance

The fungicide fluxapyroxad (BAS 700 F) has been shown to significantly increase the incidence of liver tumours in male Wistar rats at dietary levels of 1500 and 3000 ppm and in female rats at a dietary level of 3000 ppm via a non-genotoxic mechanism. In order to elucidate the mode of action (MOA) for fluxapyroxad-induced rat liver tumour formation a series of in vivo and in vitro investigative studies were undertaken. The treatment of male and female Wistar rats with diets containing 0 (control), 50, 250, 1500 and 3000 ppm fluxapyroxad for 1, 3, 7 and 14 days resulted in a dose-dependent increases in relative weight at 1500 and 3000 ppm from day 3 onwards in both sexes, with an increase in relative liver weight being also observed in male rats given 250 ppm fluxapyroxad for 14 days. Examination of liver sections revealed a centrilobular hepatocyte hypertrophy in some fluxapyroxad treated male and female rats. Hepatocyte replicative DNA synthesis (RDS) was significantly increased in male rats given 1500 and 3000 ppm fluxapyroxad for 3 and 7 days and in female rats given 50–3000 ppm fluxapyroxad for 7 days and 250–3000 ppm fluxapyroxad for 3 and 14 days; the maximal increases in RDS in both sexes being observed after 7 days treatment. The treatment of male and female Wistar rats with 250–3000 ppm fluxapyroxad for 14 days resulted in significant increases in hepatic microsomal total cytochrome P450 (CYP) content and CYP2B subfamily-dependent enzyme activities. Male Wistar rat hepatocytes were treated with control medium and medium containing 1–100 μM fluxapyroxad or 500 μM sodium phenobarbital (NaPB) for 4 days. Treatment with fluxapyroxad and NaPB increased CYP2B and CYP3A enzyme activities and mRNA levels but had little effect on markers of CYP1A and CYP4A subfamily enzymes and of the peroxisomal fatty acid β-oxidation cycle. Hepatocyte RDS was significantly increased by treatment with fluxapyroxad, NaPB and 25 ng/ml epidermal growth factor (EGF). The treatment of hepatocytes from two male human donors with 1–100 μM fluxapyroxad or 500 μM NaPB for 4 days resulted in some increases in CYP2B and CYP3A enzyme activities and CYP mRNA levels but had no effect on hepatocyte RDS, whereas treatment with EGF resulted in significant increase in RDS in both human hepatocyte preparations. Hepatocytes from male Sprague-Dawley wild type (WT) and constitutive androstane receptor (CAR) knockout (CAR KO) rats were treated with control medium and medium containing 1–16 μM fluxapyroxad or 500 μM NaPB for 4 days. While both fluxapyroxad and NaPB increased CYP2B enzyme activities and mRNA levels in WT hepatocytes, only minor effects were observed in CAR KO rat hepatocytes. Treatment with both fluxapyroxad and NaPB only increased RDS in WT and not in CAR KO rat hepatocytes, whereas treatment with EGF increased RDS in both WT and CAR KO rat hepatocytes. In conclusion, a series of in vivo and in vitro investigative studies have demonstrated that fluxapyroxad is a CAR activator in rat liver, with similar properties to the prototypical CAR activator phenobarbital. A robust MOA for fluxapyroxad-induced rat liver tumour formation has been established. Based on the lack of effect of fluxapyroxad on RDS in human hepatocytes, it is considered that the MOA for fluxapyroxad-induced liver tumour formation is qualitatively not plausible for humans.

Spirulina versus metformin for controlling some insulin signaling pathway genes in induced polycystic ovary syndrome rat model

Polycystic ovary syndrome (PCOS) is a prevalent endocrinologic and gynecologic disorder that affects women of reproductive age; besides, insulin resistance (IR) occurs in 50–70 % of PCOS cases. Metformin (Met) is commonly prescribed for IR management; however, it does not affect IR with some gastrointestinal symptoms. Spirulina platensis (SP) is a blue-green alga that may increase insulin sensitivity. Therefore, our study aims to evaluate SP as an alternative treatment to Met for improving glucose homeostasis by assessing the expression of 11 crucial genes involved in the insulin signaling pathway. After induction of the PCOS model using dehydroepiandrosterone (DHEA) (60 mg/kg bwt) for 30 consecutive days, rats were allocated into six groups. Relative liver weight, glutamic pyruvic transaminase (GPT) serum levels, glutamic-oxaloacetic transaminase (GOT), and insulin were determined. Furthermore, the gene expression of Ins1, Irs1, Pik3ca, Prkcz, Foxo1, Srebf1, Ppargc1a, Pklr, Gk, G6pc, and Pepck in the rat's liver tissue was determined using qRT-PCR. Treatment of the PCOS control group with Met or SP revealed a decrease in all these parameters compared with the PCOS model. Additionally, we found a statistically significant difference in the expression of both the Gk and Prkcz genes. To summarize our study results, SP or Met supplementation to PCOS rats had almost the same effect on assessed relative liver weight, GOT, GPT, and insulin levels compared with PCOS control rats. If further studies confirm and detect more impact of SP on IR in PCOS, SP could be used instead of Met since the latter causes many side effects.

Hepatic toxicity induced by dietary treatment of rats with hexaconazole: insights from a cytotoxic and genotoxic study

ABSTRACT Hexaconazole (HEX), a widely used triazole fungicide in agriculture, was investigated for its hepatotoxic effects on albino Wistar rats. Compared to the control rats, the treated rats showed a significant increase in absolute and relative liver weight over both 3 months (p < 0.05) and 6 months (p < 0.001). Oxidative biomarkers indicated a notable rise in malondialdehyde (MDA) by 137% (p < 0.001), increased reduced glutathione (GSH) by 32% (p < 0.01), and significant reductions in antioxidant enzymes, including a 63% decrease in catalase (CAT, p < 0.001) and a 15% decrease in superoxide dismutase (SOD, p < 0.01). Glutathione-S-transferase (GST) levels also decreased significantly after 3 and 6 months (p < 0.05). The micronucleus test in liver cells indicated an elevation in the appearance of micronuclei in rats treated with HEX for 6 months (p < 0.01). This study demonstrates, for the first time, that HEX can induce genotoxicity in the liver.