The Possible Protective Effect of Taurine on Bisphenol: Induced Structural Changes on the Cerebral Cortex of Rats: Histological and Immunohistochemical Study.

INTRODUCTION: Bisphenol A (BPA) is a chemical compound that has been used in many industries, such as paints and dental sealants. Taurine is a semi-essential amino acid with antioxidant, anti-inflammatory, and anti-apoptotic actions. AIM: This study aimed to evaluate the possible protective effect of taurine on BPA-induced structural changes in the cerebral cortex of rats using histological and immunohistochemical methods. MATERIALS AND METHODS: 35 Wistar rats (180-200 gm) were divided into control: 10 rats; Group I: 5 rats received corn oil (0.5 mL/day); Group II (Bisphenol low dose; BPAL): 5 rats received a low dose of BPA (25 mg/kg/three times/week); Group III (Bisphenol high dose; BPAH): 5 rats received a high dose of BPA (100 mg/kg/ three times/week; Group IV: (BPAL + taurine): 5 rats received taurine 100 mg/kg/day and BPAL (25 mg/kg/three times/week); Group V: (BPAH + taurine): 5 rats received taurine 100mg/kg/day and BPH (100 mg/kg/ three times/week). RESULTS: BPAL& BPAH groups showed significant dose-dependent histological changes of the neuropil, pyramidal, and neuroglial cells at H&E stained sections, significantly increased GFAP, caspase-3 immunohistochemical reaction with cells positive for Ki67 with many mitotic figures. BPAL + taurine and BPAH + taurine groups showed amelioration of the previously mentioned results. CONCLUSION: Taurine ameliorated the structural changes induced by BPA in the cerebral cortex of rats.

Histomorphological and Immunohistochemical Study of Dacomitinib-Induced Ileal Mucositis in Rats with the Possible Protection by Baicalin.

Introduction: Gastrointestinal (GIT) mucositis is a common problem associated with chemotherapy. Dacomitinib is a chemotherapeutic drug that treats nonsmall cell lung cancer. It irreversibly binds to the receptors at the ileal epithelial cells, leading to mucosal injury. Baicalin (BA) is a flavonoid with anti-inflammatory, antifibrosis, and antibarrier disruption properties. Aim: This work aimed to investigate the possible protective effects of BA on dacomitinib-induced ileal mucositis in rats by histological and immunohistochemical studies. Materials and Methods: 60 Wistar rats (8-12 weeks) were used (180-200 g) and divided into 6 groups (10 rats each). Group 1: Control; Group 2 (dacomitinib): Rats received dacomitinib 7.5 mg/kg/day orally; Group 3 (dacomitinib + carboxyl methylcellulose [CMC]): Rats received dacomitinib 7.5 mg/kg/day and 0.5% CMC orally; Group 4 (dacomitinib + BA low dose): Rats received low-dose BA 30 mg/kg/day and 7.5 mg/kg/day dacomitinib orally; Group 5 (dacomitinib + BA mid dose): Rats received mid-dose BA 60 mg/kg/day and 7.5 mg/kg/day dacomitinib orally; Group 6 (dacomitinib + BA high dose): Rats received high-dose BA 100 mg/kg/day and 7.5 mg/kg/day dacomitinib orally. Results: Dacomitinib group showed short villi, desquamated epithelium, congested blood vessels, inflammatory cellular infiltrations, dilated lacteals, and wide spaces between the crypts. There is a significant increase in collagen fibers and number of tumor necrosis factor-alpha and proliferating cell nuclear antigen-positive cells. Further, there were lost epithelial cadherin (E-cadherin) and epidermal growth factor receptor immunohistochemical reaction. The previous findings were ameliorated by BA in a dose-dependent manner. Conclusion: BA has a protective effect through its anti-inflammatory, antifibrosis, and antibarrier disruption effects. Hence, BA is considered as a promising new drug for the treatment of chemotherapy-associated GIT problems, especially dacomitinib.

Vinpocetine's immunomodulating, anti-oxidant, anti-inflammatory, ant-ifibrotic, and PDE inhibiting potencies ameliorate bleomycin-induced pulmonary fibrosis.

Objectives: Pulmonary fibrosis (PF) is a global health problem with a high economic burden. Intratracheal administration of bleomycin is the best model that resembles the pathogenesis of PF in humans. Recently, vinpocetine proved to have neuroprotective, cardioprotective, hepatoprotective, anti-aging, and antifibrotic effects through its anti-oxidant, immunomodulating, and anti-inflammatory activities. The present study investigated the antifibrotic potentiality of vinpocetine in a rat model of PF induced by intratracheal bleomycin administration. Materials and Methods: PF induced by a single intratracheal instillation of 5 mg/kg bleomycin in nine-week-old Wister rats. Oral vinpocetine was used at doses of 5, 10, or 20 mg/kg to treat PF for 21 days immediately after the bleomycin instillation. Results: Vinpocetine dose-dependently ameliorates PF induced by bleomycin administration since vinpocetine effectively restored the normal body weight gain rates, pulmonary architecture, and collagen fiber distribution and suppressed the elevated BALF cell count, lymphocytes and neutrophils percentage, BALF, IL-6, TNF-α, and TGF-ß1 levels and LDH activity, lung tissue MDA level, PDE activity, hydroxyproline content, immunohistochemical expression of α-SMA and CD68 positive macrophage, and fibrosis score. Meanwhile, it efficiently augmented the reduced BALF macrophage percentage, IL-10 level, lung tissue GSH level, CAT, and SOD activities. Conclusion: Vinpocetine may propose a new promising agent to manage PF.

Fraxetin prevented sodium fluoride-induced chronic pancreatitis in rats: Role of anti-inflammatory, antioxidant, antifibrotic and anti-apoptotic activities.

Chronic pancreatitis is considered a common gastrointestinal disorder, with significant morbidity and mortality. Fluoride is an important agent for the development of our body systems, especially for bone and teeth, however on its excess consumption, it deposits in different body tissues, especially the pancreas, causing its chronic inflammation and destruction. Fraxetin proved to possess versatile activities including; antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic activities. In the present study, we have evaluated the fraxetin potentiality to prevent fluoride-induced chronic pancreatitis in rats, by evaluating animal body weights and body weight gain rate, serum amylase, and lipase activities, pancreatic oxidative stress markers, cytokines, apoptotic markers, myeloperoxidase, and hydroxyproline levels, and histopathological changes. Nine-weeks-old male Wistar rats drank distilled water containing 500 ppm sodium fluoride (NaF) for 60 days to induce chronic pancreatitis. Oral fraxetin (20, 40, and 80 mg/kg/day) received simultaneously to prevent chronic pancreatitis development. Fraxetin in a dose-dependent manner alleviated chronic pancreatitis induced by NaF, as it restored the decreased body weight and weight gain rate, decreased the elevated serum amylase and lipase activities, pancreatic IL-6, TNF-α, MDA, caspase-3, MPO and hydroxyproline levels, and Bax/Bcl-2 ratio, enhanced pancreatic CAT and SOD activities, and GSH levels, besides it augmented the elevated IL-10 level, with the restoration of normal pancreatic architecture. Therefore, fraxetin could be a promising agent recommended for the prevention of fluoride-induced chronic pancreatitis in endemic areas.

The Possible Protective Effect of Apple Cider Vinegar on Mercuric Chloride-Induced Changes on Rat Hepatocytes: Immunohistochemical and Ultrastructure Study.

INTRODUCTION: Mercuric chloride is a toxic form of mercury capable for induction of oxidative liver damage. Apple cider vinegar (ACV) is a powerful antioxidant agent being used in salad dressings. Our study aimed to assess the beneficial effect of ACV against mercuric chloride-induced hepatic cell damage through an ultrastructural and immunohistochemical study. MATERIALS AND METHODS: Forty Wistar rats used divided into four groups (10 rats each); control; Group A (ACV): Rats received 2 ml/kg ACV; Group B (HgCl2): Rats received 1 mg/kg HgCl2, and Group C (ACV + HgCl2): Rats received 2 ml/kg ACV 30 min before giving 1 mg/kg HgCl2. Doses given orally by intragastric tube for 30 days. RESULTS: Toluidine blue results of HgCl2 group revealed hepatocytes with irregular boundaries, eccentric deeply stained nuclei, and large cytoplasmic vacuoles. Electron microscopic results showed dilated rough endoplasmic reticulum, and smooth endoplasmic reticulum, cytoplasmic vacuolations, areas of cytoplasmic rarefaction, degenerated mitochondria, nuclear membrane irregularities, and dilated bile canaliculi with lost microvilli. Moreover, there was significantly increased expression of HSP60 and number of hepatocytes with proliferating cell nuclear antigen-positive nuclei. ACV + HgCl2 group showed improvement of the previous changes. CONCLUSION: ACV could be promising for attenuation of liver cell damages induced by several toxins through its powerful antioxidant properties.

Fisetin and telmisartan each alone or in low-dose combination alleviate OVA-induced food allergy in mice.

BACKGROUND: Food allergy (FA) is a worldwide health problem, affecting nearly 10% of all populations, with no prophylactic options or regulatory treatment available until now. Fisetin, a biologically active flavonoid, and telmisartan, the highly selective competitive AT1 receptor antagonist, recently exhibited potent anti-inflammatory and immunomodulatory activities. In the present study, we have evaluated the possible anti-inflammatory and immunomodulatory activities of fisetin and telmisartan each alone or in low-dose combination in a mouse model of FA. METHODS: For induction of FA, eight-week-old BALB/c mice, sensitized by two ip injection of 50 µg ovalbumin (OVA) and 1 mg alum at day 0 and 7. Then, each mouse challenged with 10 mg OVA at days 14, 16, 18, and 21. On the 28th day, the fifth challenge carried out by oral administration of 50 mg OVA. Either fisetin (1 or 3 mg/kg/d), telmisartan (1 or 3 mg/kg/d) or a combination of fisetin 1 mg/kg/d and telmisartan 1 mg/kg/d received orally from the 13th day till 28th day. In challenge days, the treatments received one-hour before the challenge. RESULTS: Our data showed that fisetin and telmisartan each alone or in low-dose combination attenuated the anaphylactic manifestation, decreased blood eosinophilic count, serum OVA-specific IgE, and IL-4 levels, the intestinal total and degranulated mast cells count, and CD4+ immunohistochemical expression. Furthermore, they enhanced the serum IFN-γ level and abrogated the intestinal histopathological changes induced by OVA in mice. CONCLUSION: Either fisetin, telmisartan or their low-dose combination could be promising in the management of FA.

Olopatadine enhances recovery of alkali-induced corneal injury in rats.

AIMS: The alkali-induced corneal injury is an ocular emergency that required an immediate and effective management to preserve the normal corneal functions and transparency. Olopatadine is a fast, topically-effective anti-allergic drug, which exhibited potent anti-inflammatory and anti-angiogenic abilities in different allergic animals' models. Therefore, this study aimed to evaluate the therapeutic effect of olopatadine on alkali-induced corneal injury in rats. MATERIALS AND METHODS: Corneal alkali injury (CI) induced in the right eyes of an eight-week-old male Wister rats, by application of 3 mm diameter filter-papers, soaked for 10 s in 1 N-NaOH, to the right eyes' corneal centers for 30 s, afterward, the filter paper removed, and the rat right eye rinsed with 20 ml normal saline. For treatment of CI, either 0.2% or 0.77% olopatadine applied topically daily for 14 days, starting immediately after the induction of CI. KEY FINDINGS: Olopatadine, in the present work, effectively and dose-dependently enhanced the corneal healing after alkali application, with significant reduction of the corneal opacity and neovascularization scores, besides, it suppressed the augmented corneal IL-1ß, VEGF, caspase-3 levels, and nuclear NF-κB immunohistochemical expression, meanwhile it abrogated the corneal histopathological changes, induced by alkali application. SIGNIFICANCE: Olopatadine appears to be a potential treatment option for alkali-induced corneal injury.

Phloretin either alone or in combination with duloxetine alleviates the STZ-induced diabetic neuropathy in rats.

Diabetic neuropathy (DN) is one of most disabling disorder complicating diabetes mellites (DM), which affects more than 50% of the all diabetic patients during the disease course. Duloxetine (DX) is one of the first-line medication that approved by FDA for management of DN, nevertheless, it is too costly and has many adverse effects. Recently, phloretin (PH) exhibited powerful euglycemic, antihyperlipidemic, antioxidant, and anti-inflammatory activities. Therefore, we investigated the in vivo possible antineuropathic activity of phloretin, besides, its modulating effects on duloxetine potency, in a rat model of DN. Twelve-week-old male Wistar rats received a single intraperitoneal injection of 55 mg/kg STZ to induce DM. Either DX (30 or 15 mg/kg dissolved in distilled water), PH (50 0r 25 mg/kg dissolved in 0.5% DMSO) or a combination of 15 mg/kg DX and 25 mg/kg PH, used daily orally for 4 weeks to treat DN, starting from the end of the 4th week of DM development, when DN confirmed. Our finding showed that both DX and PH dose-dependently improved behavioral parameters (with the superiority of DX), sciatic nerve tissue antioxidant state, and suppressed tissue inflammatory cytokine, besides, they abrogated the tissue histopathological changes (with the superiority of PH). Moreover, DX augmented the DM metabolic disturbance and hepatic dysfunction, however, PH effectively amended these disorders. Furthermore, the low-dose combination of both, had the merits of both medications, with the alleviation of their disadvantages. Therefore, phloretin could be a promising agent in the management of DN either alone or in combination with duloxetine.

Electric injury-induced Purkinje cell apoptosis in rat cerebellum: Histological and immunohistochemical study.

INTRODUCTION: Electrical injury is a prominent problem in low income countries with increased morbidity and mortality rate. Nervous system is one of the most susceptible systems to electrical current because of its low resistance. There were different studies demonstrated electrocution effect on the nervous system, however little was made on the cerebellum. AIM: This study was conducted to produce an experimental suggestion concerning injury of the nervous system through evaluating Purkinje cell apoptosis and number in rat cerebellum by fatal and non-fatal electric current using histological and immunohistochemical study. Also to support the diagnosis of electrocution as a probable cause of death and delayed neurological damage as well as disability. MATERIALS & METHODS: Fifty male Wistar rats were divided into five groups (10 rats each); control group: normal rats that were sacrificed without exposure to electric current, groups 1-3 (non-fatal electrocution groups): rats were exposed to alternating electric current (220v, 50Hz) for one minute then were sacrificed immediately, after 2h, and after 4h respectively, and group 4 (fatal electrocution group): rats were sacrificed after being electrified up to death (153±27s). Sections from cerebellum were processed for histological and caspase-3 immunohistochemical study. RESULTS: Purkinje cells showed marked histopathological changes in the form of shrunken dark stained cells with significant reduction of their number in H &E stained sections when compared to control, widespread argyrophilia, and degenerated organelles along with shrunken irregular nuclei. For caspase-3 staining, there was significantly increased number of caspase-3 positive cells in groups 1-3 (non-fatal electrocution groups) and markedly increased in group 4 (fatal electrocution group) in comparison to control group. These changes were gradually increased with the increased duration after exposure to the electric current. CONCLUSION: Apoptosis and loss of Purkinje cells were involved in the pathogenesis of immediate and long term effect of electrical injury on Purkinje cells, which will be an aid to the forensic pathologist to determine the cause of death and residual damage as well as disability after electric shock.

Carvedilol suppresses circulating and hepatic IL-6 responsible for hepatocarcinogenesis of chronically damaged liver in rats.

Carvedilol is an anti-oxidant non-selective ß-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin. Nine-week-old male Wistar rats injected intraperitoneal by 1ml/kg 10% CCL4 in olive oil three times/week (every other day) for 12weeks to induce hepatic cirrhosis. Carvedilol (10mg/kg/day suspended in 0.5% CMC orally), silymarin (50mg/kg/day suspended in 0.5% CMC orally) or combination of both used to treat hepatic cirrhosis from 15th to 84th day. Our data showed that carvedilol and silymarin co-treatment each alone or in combination efficiently reduced the elevated serum IL-6, ALT, AST, ALP and BIL, hepatic IL-6, STAT-3, MDA levels and hydroxyproline content. In addition, it elevated the reduced serum ALB level, hepatic CAT activity and GSH level. Meanwhile, it apparently restored the normal hepatic architecture, collagen distribution and immunohistochemical E & N-cadherin expression. Furthermore, carvedilol was superior to silymarin in improving MDA level. Moreover, the combination of carvedilol and silymarin showed an upper hand in amelioration of the CCL4 induced hepatotoxicity than each alone. Therefore, carvedilol could be promising in prevention of hepatocarcinogenesis in chronic hepatic injuries.

Garlic oil inhibits dextran sodium sulfate-induced ulcerative colitis in rats.

AIMS: Garlic oil (GO) is used for centuries in folk medicine as a therapy for many diseases including inflammatory disorders. Recently, it has exhibited potent anti-oxidant, anti-inflammatory and immunomodulatory effects. Consequently, we evaluated the possible protective effect of GO in a rat model of colitis, induced by dextran sulfate sodium (DSS). MAIN METHODS: Colitis induced by allowing rats a free access to drinking water containing 5% DSS for 7 days, from day 1 to day 7. GO was administered orally in doses of 25, 50 and 100mg/kg/day. Mesalazine used as a standard medication in a dose of 15 mg/kg/day. All animals fasted for 2h, 1h before and 1h after giving the treatment, which introduced daily for 7 days, from day 1 to day 7, at 10:00 to 11:00 A.M. Animal body, and colonic weights, colonic myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, colonic reduced-glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-10 levels, macroscopic and microscopic changes of colonic tissues were evaluated. KEY FINDINGS: GO treatment significantly suppressed the elevated colonic weight, MPO activity, MDA, TNF-α and IL-1ß levels. However, it potentiated the decrease body weight, colonic SOD activity, GSH and IL-10 levels. Moreover, it ameliorated the marked macroscopic and microscopic changes of colonic mucosa in a dose dependent manner. SIGNIFICANCE: Garlic oil inhibits DSS-induced colitis in rats may be through its anti-oxidant, anti-inflammatory and immunomodulatory properties. Therefore, GO could be a promising protective agent recommended for UC patients.

The possible protective effect of simvastatin and pioglitazone separately and in combination on bleomycin-induced changes in mice thin skin.

Bleomycin is a chemotherapeutic agent with side effects especially on skin. Simvastatin is a cholesterol-lowering drug with immunomodulatory, anti-inflammatory, and antifibrotic effects. Pioglitazone is a peroxisome proliferator-activated receptor-γ antidiabetic agent with antiproliferative effects on smooth muscle cells (SMCs), and antioxidant and anti-inflammatory actions. The aim of this study was to investigate the anti-inflammatory and antifibrotic efficiencies of simvastatin and pioglitazone separately and in combination against bleomycin-induced changes in mice thin skin using histological, immunohistochemical, and biochemical techniques. In this study, the mice were divided into seven groups, with each group undergoing treatment for 3 weeks: the control group, group 1 was administered 100 µl of bleomycin, group 2 was administered simvastatin (5mg/kg/day), group 3 received pioglitazone (10mg/kg/day), group 4 received simvastatin (5mg/kg/day) 1h before bleomycin, group 5 received pioglitazone (10mg/kg/day) 1h before bleomycin, and group 6 was administered simvastatin (5mg/kg/day) and pioglitazone (10mg/kg/day) 1h before bleomycin. In group 2, dermal thickening, subcutaneous fat atrophy, degeneration of hair follicles, and thickening of cutaneous vessel walls were observed in addition to a significant increase in caspase-3 reaction, transforming growth factor beta 1 (TGF-ß1) expression, and hydroxyproline content. A reversal of the previous findings was markedly observed in group 6 compared with groups 4 and 5. We conclude that the concurrent administration of pioglitazone and simvastatin enhanced their beneficial effects in the reversal of bleomycin-induced changes in mice thin skin.