Direct and indirect antiparasitic effects of chloroquine against the virulent RH strain of Toxoplasma gondii: An experimental study.

BACKGROUND: Toxoplasmosis is a deleterious parasitic disease with harmful impact on both humans and animals. The present study was carried out to evaluate the antiparasitic effect of chloroquine (CQ), spiramycin (SP), and combination of both against the highly virulent RH HXGPRT (-) strain of Toxoplasma gondii (T. gondii) and to explore the mechanisms underlying such effect. METHODS: We counted the tachyzoites in the peritoneal fluid and liver smears of mice and performed scanning and transmission electron microscopy and immunofluorescence staining of tachyzoites. Moreover, relative caspase 3 gene expression was measured by real time polymerase chain reaction of liver tissues and immunoassay of anti-apoptotic markers [B cell lymphoma-2 (Bcl-2) and X-chromosome linked inhibitor of apoptosis (XIAP)] and interferon gamma (IFN-γ) was done in liver tissues by ELISA. In addition, we estimated serum levels of aspartate transaminase (AST) and alanine transaminase (ALT) and performed histopathological examination of liver sections for scoring of inflammation. RESULTS: We found that both CQ and CQ/SP combination significantly reduced parasitic load in the peritoneal fluid and liver smears, induced apical disruption of tachyzoites, triggered host cell apoptosis through elevation of relative caspase 3 gene expression and suppression of both Bcl-2 and XIAP. Also, they upregulated IFN-γ level, reduced serum AST and ALT, and ameliorated liver inflammation. CONCLUSIONS: Either of CQ and CQ/SP combination was more effective than SP alone against T. gondii with the CQ/SP combination being more efficient. Therefore, adding CQ to other anti-Toxoplasma therapeutic regimens may be considered in future research.

Niosomal versus nano-crystalline ivermectin against different stages of Trichinella spiralis infection in mice.

Ivermectin (IVM) is one of the competitive treatments used for trichinellosis. However, several studies linked its efficacy with early diagnosis and administration to tackle the intestinal phase with limited activity being recorded against encysted larvae. The aim of this study was to employ niosomes for enhancing effectiveness of oral IVM against different stages of Trichinella spiralis (T. spiralis) infection with reference to nano-crystalline IVM. Mice were randomized into four groups: group Ι, 15 uninfected controls; group ΙΙ, 30 infected untreated controls; group ΙΙΙ, 30 infected nano-crystalline IVM treated, and group ΙV, 30 infected niosomal IVM treated. All groups were equally subdivided into 3 subgroups; (a) treated on the 1st day post infection (dpi), (b) treated on the 10th dpi, and (c) treated on the 30th dpi. Assessment was done by counting adult worms and larvae plus histopathological examination of jejunum and diaphragm. Biochemical assessment of oxidant/antioxidant status, angiogenic, and inflammatory biomarkers in intestinal and muscle tissues was also performed. Both niosomes and nano-crystals resulted in significant reduction in adult and larval counts compared to the infected untreated control with superior activity of niosomal IVM. The superiority of niosomes was expressed further by reduction of inflammation in both jejunal and muscle homogenates. Biochemical parameters showed highly significant differences in all treated mice compared to infected untreated control at different stages with highly significant effect of niosomal IVM. In conclusion, niosomal IVM efficacy exceeded the nano-crystalline IVM in treatment of different phases of trichinellosis.

Lycopene ameliorates the effect of Aroclor 1254 on morphology, proliferation, and angiogenesis of the thyroid gland in rat.

Aroclor 1254 is a mixture of polychlorinated biphenyls that are reported to disrupt thyroid hormone homeostasis, yet little is known on its effect on thyroid gland microarchitecture. Lycopene is a commonly used potent antioxidant. This study is a biochemical, histological, and immunohistochemical assessment of the effect of Aroclor 1254 on the morphology, proliferation, and angiogenesis of the thyroid gland in rat and to evaluate the possible ameliorating role of lycopene. Twenty-four adult male albino rats were divided into 4 groups; Control, lycopene-treated (4 mg/kg/day orally for 30 days), Aroclor 1254-treated (2 mg/kg/day intraperitoneally for 30 days), and lycopene & Aroclor 1254-treated group. Serum thyroid hormones, thyroid-stimulating hormone (TSH), and tissue malondialdehyde (MDA) were quantified. Thyroid specimens were processed for histological staining with hematoxylin and eosin, periodic acid-Schiff, and Mallory's trichrome stains as well as immunohistochemical staining for detection of calcitonin, Ki67, and VEGF. In this study, Aroclor 1254-treated animals recorded a significant decline in both serum T3 and T4 coupled with a significant elevation in both TSH and tissue MDA. Histological sections showed small irregular follicles with the formation of hyperplastic and micro follicles. Some follicular and parafollicular cells depicted nuclear and cytoplasmic alterations associating with scanty or absent colloid in addition to signs of inflammation and fibrosis. A significant upregulation in the immunohistochemical expression of calcitonin, Ki67, and VEGF was recorded. Lycopene co-treatment successfully reinstated the values of most studied parameters and retrieved a near-control thyroid morphology. In conclusion, Aroclor 1254 impacted the thyroid hormone homeostasis, morphology, proliferation, and angiogenesis of the thyroid gland in rat, while lycopene efficiently ameliorated these adverse effects.

Oxidative stress mediated apoptotic potential of mefloquine on experimental trichinellosis.

Conventional anthelmintics such as albendazole could not achieve complete cure of trichinellosis till now. The antimalarial mefloquine mediates oxidative stress and disrupts lysosomal functions leading to cell death. Therefore, the aim of this work was to investigate the effect of mefloquine on experimental acute and chronic trichinellosis and to clarify the possible mechanisms of such effects. Mice were divided into four groups; Group I: Uninfected untreated control (20 mice); Group II: Infected untreated control (40 mice); Group III: infected and treated with albendazole (400 mg/kg) (40 mice); Group IV: infected and treated with mefloquine (300 mg/kg) (40 mice). All infected treated groups were equally subdivided into 2 subgroups; (a) treated on the 2nd day post infection (dpi) for 3 days, (b) treated on the 35th dpi for 5 days. Parasitological adults and larvae counting besides immunohistopathological examination of intestines and muscles were done. Biochemical assay of oxidant/antioxidant status, apoptotic, cytoprotective and inflammatory biomarkers in intestinal and muscle homogenates were achieved. Results showed that both albendazole and mefloquine significantly reduced adults and larvae counts with higher efficacy of albendazole in the intestinal phase and superiority of mefloquine in the muscle phase. The superiority of mefloquine was indicated by increased inflammatory immune infiltration and decreased anti-apoptotic immunohistochemical markers expression in both jejunal and muscle tissues. Biochemically, mefloquine treatment showed highly significant oxidative, apoptotic and inflammatory effects. So, our results suggest that mefloquine might be a superior treatment for chronic trichinellosis.

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.

Metformin ameliorated methotrexate-induced hepatorenal toxicity in rats in addition to its antitumor activity: two birds with one stone.

Methotrexate (MTX) is a drug used in treatment of various malignancies. Unfortunately, it leads to life-threatening complications including hepatorenal toxicity. Previous studies revealed the protective effects of metformin (MET) on hepatorenal toxicity in other models in addition to its anticancer effects. The current study investigates the effect of MET on MTX-induced hepatorenal toxicity and the possible mechanisms involved in this toxicity which can be overwhelmed by MET. Thirty male rats were divided into 3 groups: normal control, MTX treated and MET/MTX treated. After 7 days, MTX induced hepatorenal toxicity as proved by histological examinations and biochemical analysis of liver and kidney functions. Also, it led to significant increase in hepatic and renal malondialdehyde levels, significant decrease in hepatic and renal total antioxidant capacity levels and Na+/K+-ATPase activities and significant up regulation of mRNA expressions of nuclear factor kappa-light-chain-enhancer of activated B cells, cyclooxygenase-2 and caspase 3 compared with the control group. While, MET could significantly reduce hepatorenal toxicity and counteract the effects of MTX on all measured parameters. In conclusion, MET can be an effective adjuvant to MTX chemotherapy that could ameliorate its hepatorenal toxicity through antioxidant, anti-inflammatory and anti-apoptotic mechanisms.