Hepatoprotective effect of astaxanthin against cholestasis liver fibrosis induced by bile duct ligation in adult Wistar rats.

In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.

Niosomal hesperidin attenuates the M1/M2-macrophage polarization-based hepatotoxicity followed chlorpyrifos -induced toxicities in mice.

Chlorpyrifos(CPF) is a well-known hepatotoxic agent that has side effects on several organs. On the contrary, hepatic macrophages are crucial in maintaining liver tissue integrity. The main objective of this study was to evaluate the effects and possible mechanisms of niosomal hesperidin (Nio + Hesp), a flavanone glycoside found in citrus fruits, on M1-M2 liver macrophage polarization and inflammatory cells in the brain, liver, and ovarian tissues. Forty C57 mice were divided into CPF(3 mg/kg), Sham(Dimethyl sulfoxide 40 µL/kg), CPF + Hesp(100 mg/kg), and CPF + Nio + Hesp (100 mg/kg) groups. The activity of sera superoxide dismutase (SOD) and malondialdehyde (MDA), brain, liver, and ovary tissues changes, and M1-M2 liver macrophage polarization were evaluated by examining the expression of CD163 and CD68 genes. Hepatic lesions consisting of sporadic foci of coagulation necrosis, inflammatory cell reaction, and regenerative fibrosis were seen following CPF injection, reflected by significant overexpression of CD163 and CD68 genes. In comparison, Nio + Hesp declined the amount of cell apoptosis in the liver and downregulated CD163 and CD68 gene expression. Both Nio + Hesp and Hesp alleviated CPF-induced hepatotoxicity, however, Nio + Hesp was superior to hesperidin in the downregulation of the CD163 and CD68 gene expression. Even though a significant difference between hesperidin and Nio + Hesp was observed in the number of Graafian follicles, corpus luteum, and peri-antral follicles, no substantial difference was observed in primary follicles. The ameliorative effects of Hesp and Nio + Hesp may be at least in part due to their antioxidant and anti-inflammatory properties. These findings showed that both M1- and M2-macrophages contributed to the development of hepatic lesions induced by CPF and provided information about macrophage activation, indicating the importance of analysis of macrophage phenotypes for hepatotoxicity based on M1/M2-polarization which can be downregulated by niosomal nesperidin.

Atheroprotective and hepatoprotective effects of trans-chalcone through modification of eNOS/AMPK/KLF-2 pathway and regulation of COX-2, Ang-II, and PDGF mRNA expression in NMRI mice fed HCD.

BACKGROUND: The effects of trans-chalcone on atherosclerosis and NAFLD have been investigated. However, the underlying molecular mechanisms of these effects are not completely understood. This study aimed to deduce the impacts of trans-chalcone on the eNOS/AMPK/KLF-2 pathway in the heart tissues and the expression of Ang-II, PDFG, and COX-2 genes in liver sections of NMRI mice fed HCD. METHODS AND RESULTS: Thirty-two male mice were divided into four groups (n = 8): control group; fed normal diet. HCD group; fed HCD (consisted of 2% cholesterol) (12 weeks). TCh groups; received HCD (12 weeks) besides co-treated with trans-chalcone (20 mg/kg and 40 mg/kg b.w. dosages respectively) for 4 weeks. Finally, the blood samples were collected to evaluate the biochemical parameters. Histopathological observations of aorta and liver sections were performed by H&E staining. The real-time PCR method was used for assessing the expression of the aforementioned genes. Histopathological examination demonstrated atheroma plaque formation and fatty liver in mice fed HCD which were accomplished with alteration in biochemical factors and Real-time PCR outcomes. Administration of trans-chalcone significantly modulated the serum of biochemical parameters. These effects were accompanied by significant increasing the expression of eNOS, AMPK, KLF-2 genes in heart sections and significant decrease in COX-2, Ang-II, and PDGF mRNA expression in liver sections. CONCLUSION: Our findings propose that the atheroprotective and hepatoprotective effects of trans-chalcone may be attributed to the activation of the eNOS/AMPK/KLF-2 pathway and down-regulation of Ang-II, PDFG, and COX-2 genes, respectively.

Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to animals: an updated review.

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19.

Effect of memantine on expression of Bace1-as and Bace1 genes in STZ-induced Alzheimeric rats.

Recent studies have showed that the long non-coding RNAs (lncRNAs) expression is dysregulated in different neurodegenerative disorders like Alzheimer's disease (AD). In the present study, the effects of memantine on the level of Bace1-as and Bace1 genes' expression in streptozotocin (STZ)-induced Alzheimer's and memantine treated rats were investigated. The male Wistar rats were randomly divided into four groups: 1-Normal control, 2-Sham-operated control, 3- Alzheimer'scontrol rats (ICV-STZ), 4-Experimental group rats treated by memantine in a dose of 30 mg/kg/day for 28 days in ICV-STZ rats. The expression of Bace1-as and Bace1 genes was measured by quantitative-PCR in the brain and blood tissues. ELISA was used to analyze Bace1 and Aß proteins. Expression of Bace1-as was significantly increased in the brain and blood tissues of the experimental group (p = 0.032 and p = 0.034, respectively). The expression of Bace1 gene showed no significant changes in the brain. Furthermore, the ELISA analysis revealed that Bace1 protein was significantly increased in the plasma of the Alzheimer's control group (p = 0.000) and in the brain tissue of the experimental group (p = 0.000). Additionally, Aß levels had no significant changes between all groups studied. The Bace1 protein may be used as a prognostic biomarker in plasma, or before using memantine as a treatment. Furthermore, Bace1-as gene expression may play a role in monitoring the progression of AD.

Effect of sinapic acid on memory deficits and neuronal degeneration induced by intracerebroventricular administration of streptozotocin in rats.

The present study aimed to elucidate the neuroprotective effect of sinapic acid on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were randomly divided into 11 groups: normal control, sham-operated control, sinapic acid (2.5, 5, 10, and 20 mg/kg bw intragastrically, daily) alone, Alzheimer control rats (ICV-STZ, 3 mg/kg bw), sinapic acid (2.5, 5, 10, and 20 mg/kg bw intragastrically, daily) together with STZ, and the treatment was performed accordingly. After 28 days of ICV-STZ administration, the animals were assessed for cognitive performance using passive avoidance test and then sacrificed for biochemical and histopathological examinations. Sinapic acid was found to be effective in improving antioxidant status and preventing memory loss in Alzheimer rats. Moreover, TNF-α level in the hippocampus was significantly decreased by sinapic acid. Also, administration of sinapic acid significantly increased the levels of antioxidant enzymes and decreased malondialdehyde level in the hippocampus. Histopathological examination showed that sinapic acid reduced cell loss in the cerebral cortex and hippocampus in Alzheimer's rats. The present study suggests that sinapic acid is effective in the prevention of memory loss and improvement of oxidative stress and might be beneficial in the treatment of Alzheimer's disease.

Effects of folic acid on dyslipidemia and serum homocysteine in a rat model of cholestasis and hepatic fibrosis.

The liver is the major site for storage and metabolism of folate. Folate deficiency is common in many liver diseases and causes severe effects on cellular metabolism and increases oxidative stress and the homocysteine (Hcy) level. The objective of this research was to investigate the effects of folic acid on dyslipidemia and serum Hcy concentrations in an experimental rat model of cholestasis. Eighty-one male Wistar rats were divided into nine groups: control, sham-operated, folic acid control, bile duct-ligated (BDL), and BDL+ folic acid groups. In folic acid treated groups, folic acid (1, 5, and 10 mg/kg body weight) was given orally for 28 days. After taking blood and liver samples, plasma lipid profiles and Hcy and hepatic reduced and oxidized glutathione concentrations were measured. Histopathological features of cholestasis were assessed by Masson's trichrome staining. Treatment of folic acid in BDL rats significantly prevented the progression of hepatic fibrosis and improved the serum and liver biochemical changes. These results suggest that folic acid protects the liver against cholestasis by reducing serum Hcy and by its antioxidant properties. Folic acid can be an important therapeutic intervention in dyslipidemia caused by cholestasis.

Hepatoprotective effects of Portulaca oleracea extract against CCl4-induced damage in rats.

CONTEXT: Purslane (Portulaca oleracea L., Portulacaceae) has been traditionally used in folk medicine to afford protection against liver injury, although its actual efficacy remains uncertain. OBJECTIVE: To evaluate purslane as a hepatoprotective agent, we investigated the protective effect of its ethanol extract against carbon tetrachloride (CCl4)-induced hepatic toxicity in rats. MATERIALS AND METHODS: A total of 108 male Wistar rats were randomly divided into 12 groups. The first group was maintained as normal control, whereas CCl4 (0.5 ml/kg bw, 50% CCl4 in olive oil, i.p.), purslane extract (0.005, 0.01, 0.05, 0.1, and 0.15 g/kg bw, intragastrically), and purslane extract (five doses as above) along with CCl4 were administered to the Groups II, III-VII, and VIII-XII, respectively. The rats were sacrificed on the 30th day, and blood was withdrawn by cardiac puncture. Liver damage was assessed by measuring hepatic marker enzymes (ALT, AST, ALP, GGT, and SOD) and histopathological observation. RESULTS: Treatment with CCl4 resulted in increased serum activities of marker enzymes with a concomitant decrease in SOD. Histological alterations were also observed in the liver tissue upon CCl4 treatment. Administration of purslane extract (0.01, 0.05, 0.1, and 0.15 g/kg b.w.) significantly showed a marked tendency towards normalization of all measured biochemical parameters in CCl4-treated rats. Histopathological changes also paralleled the detected alteration in markers of liver function. DISCUSSION AND CONCLUSION: These results demonstrate that purslane exerts protective effects against CCl4-induced damage in rat liver and supports a potential therapeutic use of purslane as an alternative for patients with liver diseases.

The effect of vitamin A and vitamin C on postoperative adhesion formation: A rat model study.

BACKGROUND: The aim of this study is to investigate the effect of vitamin A and C, as the agents that improve wound healing, on the adhesion formation process. MATERIALS AND METHODS: Sixty male Wistar rats were used. They underwent midline laparotomy, for repair of a peritoneal injury, and were then assigned to four groups. Group 1 (Vitamin A) received 2000 units/kg intramuscular injection of vitamin A daily, post surgery, for two weeks; Group 2 (Vitamin C) received 100 mg/kg oral vitamin C daily, after laparotomy, for two weeks; Group 3 (vitamins A and C) received 2000 units/kg intramuscular injection of vitamin A and 100 mg/kg oral vitamin C daily, after laparotomy, for two weeks, and Group four (Sham) rats did not receive any drugs. The adhesion, inflammation, fibrosis scores, and wound integrity were evaluated after two weeks. RESULTS: Rats in the vitamin C group had the lowest mean adhesion formation score (1 ± 0.27) and the values of p were < 0.0001 for the vitamin A group and vitamin A and C groups and 0.003 for the sham group. Vitamin C also had the lowest fibrosis score (0.50 ± 0.17) among the study groups and the values of p were < 0.0001 for the vitamin A group and vitamin A and C groups and 0.002 for the sham group. The mean inflammation score did not differ significantly among the study groups. The wound disruption strength was the highest in the vitamin C group and the difference was statistically significant in the sham group (1188.69 ± 281.92 vs. 893.04 ± 187.46, p : 0.003). CONCLUSION: Administration of oral vitamin C reduces adhesion formation and improves wound healing.

Nanoselenium attenuates renal ischemia-reperfusion injury in rats.

Using selenium (Se) nanoparticles has received attention in recent years because of their therapeutic benefits due to their anticancer, antioxidant, anti-inflammatory, and anti-diabetic effects. This research was conducted to evaluate the possible protective impact of nano-Se on renal unilateral ischemia/reperfusion injury (uIRI) in adult male Wistar rats. Using clamping of the left renal pedicle within 45 min uIRI was induced. The animals were randomly divided into nine groups of control, nano-Se (0.25, 0.5, and 1 mg/kg bw/day) alone, uIRI control, and uIRI rats administrated with nano-Se. At 30 days after treatment, the animals were sacrificed to be assessed biochemically and histopathologically. Nano-Se in uIRI groups have significantly decreased serum creatinine, urea levels, renal histological damage, and increased antioxidant status. Also, our findings demonstrated that the administration of nano-Se caused a significant decrease in the immunoreactivity level of the epidermal growth factor (EGF) and EGFR expression (EGF receptor) in the renal tissue of the uIRI rats. Therefore, nano-Se possesses renoprotective effects, and this effect might be attributable to its antioxidant and free radical scavenger effects. These renoprotective effects may depend on the decreased EGF immunoreactivity level and EGFR expression in the kidney tissue and improve the structure of the kidney tissue. Thus, our research provided biochemical and histological data supporting the potential clinical use of nano-Se for the treatment of certain kidney disorders.

Canine Mammary Tumors as a Potential Model for Human Breast Cancer in Comparative Oncology.

Clinical and molecular similarities between canine mammary tumors (CMTs) and human breast cancer (HBC) propel scientists to further study their application in comparative oncology as a model for human breast cancer. In total, 64 canine mammary tumors were selected to study the most common markers, which are applicable for human breast cancer treatment, including estrogen and progesterone receptors (ER and PR), human epidermal growth factor (HER2/neu), Ki67, and cyclooxygenase 2 (Cox2). Immunohistochemistry (IHC) was used to assess the protein expression. The Veterinary Nottingham Prognostic Index (Vet-NPI) was also computed. Moreover, univariate and multivariable Cox proportional hazard analyses were applied to estimate hazard ratios (HRs). The results demonstrated that Ki67 was strongly expressed in the triple-negative tumors, and Ki67 protein expression continuously increased over the increase of Cox2 protein expression (p < 0.001). Further analysis revealed a significant difference among canine mammary subtypes and Vet-NPI, in which triple-negative tumors displayed the highest mean score compared to other subtypes (p < 0.001). In addition, the multivariable analysis revealed that the regional mastectomy procedure (adjusted HR = 2.78 (1.14-6.8)), the triple-negative tumors (adjusted HR = 48.08 (7.74-298.8)), strong Ki67 protein expression group (adjusted HR = 7.88 (2.02-30.68)), and strong Cox2 protein expression group (adjusted HR = 29.35 (5.18-166.4)) demonstrated significantly lower disease-free survival rates compared to other corresponding groups. Overall, canine mammary tumors showed strong similarities to human breast cancer in terms of clinical and molecular aspects; therefore, they could be suggested as a model for human breast cancer in comparative oncology.

Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats.

CONTEXT: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. OBJECTIVE: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl4)-induced liver damage in rats. MATERIALS AND METHODS: The rats were randomly divided into seven groups: control, CCl4 (i.p., 0.5 mL/kg b.w., 50% CCl4 in olive oil), walnut extract (at dose level of 0.2 g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4 g/kg b.w.) with CCl4, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation. RESULTS: Administration of walnut leaf extract (ranging from 0.2 to 0.4 g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl4-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl4-treated rats. DISCUSSION AND CONCLUSION: These results suggest that walnut extract has a protective effect over CCl4-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.

Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research.

BACKGROUND: Breast cancer is one of the most common malignancies in women, with one in 20 globally. Oncolytic viruses have recently been the first step in the biological treatment of cancer, either genetically engineered or naturally occurring. They increase specifically inside cancer cells and destroy them without damaging normal tissues or producing a host immune response against tumour cells or expressing transgenes. One of the most known members of this family is the Newcastle disease virus (NDV), a natural oncolytic virus that selectively induces apoptosis and DNA fragmentation in human cancer cells. METHODS: This study performed biochemical and molecular investigations with variable doses of NDV (32, 64, 128 HAU) and liposomal doxorubicin (9 mg/kg) on mouse triple-negative mammary carcinoma cell line 4T1 and BALB/c models tumours for the first time. RESULTS: Real-time quantitative PCR analysis in NDV-treated animal tumours showed increased expression of P21, P27 and P53 genes and decreased expression of CD34, integrin Alpha 5, VEGF and VEGF-R genes. Additional assessments in treated mouse models also showed that NDV increased ROS production, induced apoptosis, reduced tumour size and significantly improved prognosis, with no adverse effect on normal tissues. CONCLUSIONS: These findings all together might indicate that NDV in combination with chemotherapy drugs could improve prognosis in cancer patients although many more conditions should be considered.

miR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.

Effect of new methionine-based ionic liquid on the CDR1 and CDR2 gene expression on sensitive and resistant strains of Candida albicans.

Background and Objectives: Previous researchers showed the antimicrobial ability of ionic liquids (ILs) on different infective agents. ILs can dissolve organic components, especially DNA molecules. Among synthesized eight binary ILs mixtures, we have chosen ([Met-HCl] [PyS]) IL for determining the antifungal ability of IL against Candida albicans cells. Materials and Methods: Well diffusion assay, chrome agar and Germ tube tests were used to detect the Candida samples. PCR, real-time-PCR, and flow cytometry tests were performed to determine the IL's rate of toxic ability. Results: Well diffusion assay revealed the diameters of the growth inhibition zones were the largest in IL with methionine and Proline amino acids. Minimum inhibitory concentration (MIC) and the Minimum fungicidal concentration (MFC) tests showed that they inhibited the growth of the C. albicans at a range from 250 µg/ml for sensitivity and 400 µg/ml for resistance, MIC average of all samples were 341.62 ± 4.153 µg/ml. IL reduced the expression of CDR1 and CDR2 the genes encoded by the major protein of ABC system transporter by 2.1 (P= 0.009) and 1.2 fold (P= 0.693), revealed by PCR and real time-PCR. In the flow cytometry test, there were increasing dead cells after treating with the ([Met-HCl] [PyS]) even in the most resistant strain. Conclusion: The novel IL was effective against the most clinical and standard C. albicans.

Hepatoprotective and antifibrotic effects of trans-chalcone against bile duct ligation-induced liver fibrosis in rats.

Objectives: Several lines of research have shown that hepatic fibrosis is one of the leading causes of death worldwide. Trans-chalcone is a flavonoid precursor with anti-oxidant and anti-inflammatory effects. The present study was conducted to examine the antifibrotic properties of trans-chalcone on bile duct ligation (BDL)-induced liver cholestasis in rats. Materials and Methods: Following the BDL operation, trans-chalcone at doses of 12, 24, and 50 mg/kg was administered orally once a day for 45 consecutive days. Serum levels of liver indices, including alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and lipid profile in addition to blood urea nitrogen (BUN) and creatinine, were measured. Additionally, catalase (CAT) and superoxide dismutase (SOD) activities were assessed in liver homogenates. Histopathological evaluations were performed using Masson trichrome (MT) and hematoxylin and eosin (H&E) staining. Results: The elevated levels of liver enzymes, total and direct bilirubin, BUN, creatinine, cholesterol, triglyceride, and low-density lipoprotein (LDL) induced by BDL were significantly reduced following trans-chalcone administration; while serum level of high-density lipoprotein (HDL) increased. Besides, treatment with trans-chalcone elevated the activities of CAT and SOD in the liver tissues of the animals with BDL surgery. According to MT and H&E staining, BDL-induced histopathological changes, including infiltration of inflammatory cells, hepatocyte necrosis, ductal hyperplasia, and collagen deposition were ameliorated using trans-chalcone administration. Conclusion: It can be concluded from the present study that trans-chalcone, possibly by its anti-oxidant and anti-inflammatory properties, may exert hepatoprotective and antifibrotic effects in BDL-induced liver fibrosis.

The comparative effects of estrogen and tacrolimus on crushed sciatic nerve regeneration in male mice: functional and histopathological evaluation.

Some pharmacological agents can be effective for peripheral nerve injuries treatments. Present study was aimed to apply different agents and to compare the nerve regenerative effects following crushed sciatic nerve injuries. Twenty-four adult male mice were conducted in this study. Standard unilateral left side sciatic nerve crush was performed with 2.00 mm width mosquito hemostat forceps. The mice were randomly divided into four groups with the same numbers in each group which received subcutaneously, estrogen (group I), tacrolimus (group II), the combination of estrogen and tacrolimus (group III), and saline 0.90%. Functional recovery, histopathology, and immunohistochemistry (IHC) were performed on days 14th and 28th. Walking track analysis on day 14th showed no significant difference between experimental groups, however, they showed significant difference compared to the control group. At the same time, experimental groups showed similar results of inflammatory cell infiltration, axonal edema, and count with significant differences compared to control group. At the end of the study, group I and III showed a significant difference in functional recovery between group II and control. After fourth week significant histopathological difference of axonal count was observed in group III. On day 28th, only IHC assessment in group III showed more glial fibrillary acidic protein (GFAP) expression compared to the same group on day 14th. This study revealed subcutaneous administration of combined estrogen and tacrolimus could be effective with acceptable results in nerve regeneration.

The Effect of Broccoli Extract in Arsenic-Induced Experimental Poisoning on the Hematological, Biochemical, and Electrophoretic Parameters of the Liver and Kidney of Rats.

Heavy metals such as arsenic contribute to environmental pollution that can lead to systemic effects in various body organs. Some medicinal plants such as broccoli have been shown to reduce the harmful effects of these heavy metals. The main aim of the present study is to evaluate the effects of broccoli extract on liver and kidney toxicity, considering hematological and biochemical changes. The experimental study was performed in 28 days on 32 male Wistar rats classified into four groups: the control group (C), a group receiving 5 mg/kg oral arsenic (AS), a group receiving 300 mg/kg broccoli (B), and a group receiving arsenic and broccoli combination (AS + B). Finally, blood samples were taken to evaluate the hematological and biochemical parameters of the liver and kidney, as well as serum proteins' concentration. Liver and kidney tissue were fixed and stained by H&E and used for histopathological diagnosis. The results demonstrated a significant decrease in white blood cells (WBC), red blood cells (RBC), and hemoglobin (Hb) in the AS group compared to other groups. However, in the B group, a significant increase in RBC and WBC was observed compared to the AS and C groups (P < 0.05). Moreover, RBC and WBC levels increased significantly in the AS + B group compared to the AS group (P = 0.046). However, in the AS group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels increased, while total protein, albumin, and globulin decreased. This can be a result of liver and kidney damage, which was observed in the AS group. Furthermore, the increase in the concentration of albumin and globulin in the AS + B group was higher than that in the AS group. Infiltration of inflammatory cells and necrosis of the liver and kidney tissue in the pathological evaluation of the AS group were significantly higher than other groups. There was an increase in superoxide dismutases (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC); however, a decrease in malondialdehyde (MDA) concentration was seen in the AS + B group compared to the AS group. It seems that broccoli is highly effective at reducing liver and kidney damage and improving the hematological and biochemical factors in arsenic poisoning conditions.

Efficacy of hyaluronic acid, absorbable collagen sponge, and their combination in minimizing bisphosphonate-related osteonecrosis of the jaws (BRONJ) after dental extraction: a preliminary animal histomorphometric study.

INTRODUCTION: There is no study on the effectiveness of hyaluronic acid (HA) placement either with or without absorbable collagen sponge (ACS) in reducing or preventing bisphosphonate-related osteonecrosis of the jaws (BRONJ). This preliminary animal study examined the efficacy of this clinically important treatment. METHODS: For simulating BRONJ, zoledronic acid was administered to 40 rats for 5 weeks. Two weeks later, a right first molar was extracted from each rat. The rats were randomized into four groups of socket treatments: control (empty extraction socket) or with sockets filled with ACS, HA, or HA+ACS (n=4×10). After 2 weeks, 5 rats in each group were sacrificed and subjected to histopathologic and histomorphometric evaluation. Eight weeks post-surgically, the rest of rats were euthanized and histologically examined. The Kruskal-Wallis test was used to compare the four treatments at each time point (α=0.05). RESULTS: Six rats were lost overall. In the second week, vascularization was higher in ACS group (P<0.05); osteoclast activity was not different between groups (P>0.05); empty lacunae were the most and fewest in control and HA+ACS groups, respectively (P<0.05); eosinophil infiltration was maximum in HA group (P<0.05); lymphocyte counts were maximum and minimum in the HA+ACS and ACS groups, respectively (P<0.05); the highest and lowest neutrophil counts were seen in ACS and control groups, respectively (P<0.05); and the extent of live bone did not differ between groups (P>0.05). In the eighth week, vascularization was not different in groups (P>0.05); the highest and lowest osteoclast activities were seen in the control and HA+ACS groups, respectively (P<0.05); empty lacunae were the most and fewest in control and HA+ACS, respectively (P<0.05); maximum and minimum numbers of eosinophils were in control and HA+ACS groups, respectively (P<0.05); HA and control groups exhibited the highest and lowest lymphocyte counts, respectively (P<0.05); the lowest and highest neutrophil counts were observed in HA+ACs and control groups, respectively (P<0.05); and the highest and lowest extents of the live bone were observed in HA+ACS and control groups, respectively (P<0.05). CONCLUSIONS: Within the limitations of this preliminary animal study, HA and especially HA+ACS seem a proper method for preventing or treating BRONJ.

Histomorphometric Effects of 2% Risedronate Gel on Calvarial Bone Defects in Rabbits.

STATEMENT OF THE PROBLEM: Alveolar bone resorption associated with periodontal disease is a common finding and generally irreversible. It impairs mastication and causes esthetic problems for patients. Bisphosphonates are the most commonly used antiresorptive agents for bone diseases. PURPOSE: Considering the risk of bisphosphonate-related osteonecrosis of the jaw, this study aimed to assess the effect of 2% risedronate gel on calvarial bone defects in rabbits. MATERIALS AND METHOD: In this animal study, critical-size defects of 8mm were created in the calvaria of 20 New Zealand white rabbits. In group 1 (n=10), 2% risedronate gel was applied into the right side defect while the left side defect remained empty and served as control. In group 2 (n=10), placebo gel was applied into the right side defect, while the left side defect remained empty and served as control. Five rabbits in each group were sacrificed at 1month and the remaining five at 2 month, post-operatively, and tissue samples were collected for histomorphometric analysis. Histomorphometric assessments included bone fill, degree of inflammation, number of osteoblasts, number of osteoclasts, and foreign body reaction at the site. Data were statistically analysed using SPSS version 25 via the Dunn test and Kruskal-Wallis test. RESULTS: No bone remodeling was noted in any group at 1 month. The risedronate group showed significantly higher bone fill than the other groups after 2 months (p= 0.016). At 2 months, the number of osteoblasts was significantly higher in the risedronate group (p< 0.05). The groups were not significantly different in terms of inflammation score at 1 (p= 0.31) or 2 (p=0.69) months. Foreign body reaction was not observed in any group at any time point. No osteoclast was detected in any group at any time point. CONCLUSION: Risedronate gel showed superior efficacy with regard to regeneration of rabbit calvarial bone defects compared to the placebo and control groups.