Multi-biomarkers approach to assess the toxicity of novel insecticide (Voliam flexi®) on Clarias gariepinus: From behavior to immunotoxicity.

This study was conducted to determine for the first time the immunological, histopathological, histochemical, and ultrastructural changes; hematological and biochemical alterations; and poikilocytosis induced in Clarias gariepinus by Voliam flexi® 40% WG (thiamethoxam + chlorantraniliprole). Beside control fish, juvenile C. gariepinus were subjected to three sublethal concentrations of Voliam flexi® (43.5, 87.5, and 175 mg/L) for 15 days. Voliam flexi® induced immunotoxic impairments in C. gariepinus, such as a decrease in some immunity variables (lysozyme and phagocyte activity, immunoglobulin concentration, and nitro blue tetrazolium level). It also caused an extreme increase in the levels of primary cytokines (interleukin-1ß and IL-6), compared with the control. The toxic effects of Voliam flexi® increased gradually with the increasing concentrations tested. Histological examination of the liver demonstrated necrosis, vacuolated hepatocytes (fatty deposition), melanomacrophage centers, foci of inflammatory cells, congested and dilated blood sinusoids, hepatic degeneration, fibrosis increment (Sirius Red stain), and glycogen depletion, as well as cytopathological alterations. We conclude that the toxic effects of Voliam flexi® must be restricted or prevented by using control mechanisms in aquatic systems.

Camel whey protein protects lymphocytes from apoptosis via the PI3K-AKT, NF-κB, ATF-3, and HSP-70 signaling pathways in heat-stressed male mice.

Heat stress (HS) is an environmental factor that depresses the immune systems that mediate dysfunctional immune cells. Camel whey protein (CWP) can scavenge free radicals and enhance immunity. This study investigated the impact of dietary supplementation with CWP on immune dysfunction induced by exposure to HS. Male mice (n = 45) were distributed among 3 groups: control group; HS group; and HS mice that were orally administered CWP (HS + CWP group). The HS group exhibited elevated levels of reactive oxygen species (ROS) and pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, tumor necrosis factor-α) as well as a significant reduction in the IL-2 and IL-4 levels. Exposure to HS resulted in impaired phosphorylation of AKT and IκB-α (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha); increased expression of activating transcription factor 3 (ATF-3) and 70 kDa heat shock proteins (HSP70); and aberrant distribution of CD3+ T cells and CD20+ B cells in the thymus and spleen. Interestingly, HS mice treated with CWP presented significantly restored levels of reactive oxygen species and pro-inflammatory cytokines near the levels observed in the control mice. Furthermore, supplementation of HS mice with CWP enhanced the phosphorylation of AKT and IκB-α; attenuated the expression of ATF-3, HSP70, and HSP90; and improved T and B cell distributions in the thymus and spleen. Our findings reveal a potential immunomodulatory effect of CWP in attenuating immune dysfunction induced by exposure to thermal stress.

Protective effects of camel whey protein against scrotal heat-mediated damage and infertility in the mouse testis through YAP/Nrf2 and PPAR-gamma signaling pathways.

Elevation of scrotal temperature is one of the most important causes of impaired spermatogenesis and male infertility, but the exact mechanism remains controversial. The present study investigated the impact of camel whey protein (CWP) on the mechanisms of heat stress (HS)-mediated testicular damage in male mice. Exposure to HS was associated with significant increase in the testicular tissues' oxidative stress. Mechanistically, exposure to HS resulted in upregulation of P53 and Nrf2 expressions; downregulation of Bcl2 and PPAR-γ expressions; and induction of testicular Leydig cell hyperplasia. Because Leydig cells produce testosterone up on stimulation with Luteinizing hormone (LH), HS mice also exhibited significant reduction in the serum testosterone levels followed by significant reduction in the percentages of progressively motile sperm and higher percentages of immotile sperm, when compared with those of control mice. Interestingly, treatment of HS mice with CWP significantly restored the levels of ROS and the activities of antioxidant enzymes in the testicular tissues nearly to those observed in control mice. Furthermore, CWP supplemented HS mice exhibited complete restoration of Bcl2, P53, Nrf2, and PPAR-γ expressions; testicular Leydig cell distribution; significant higher levels of testosterone levels; and hence higher percentages of progressively motile sperm and lower percentages of immotile sperm as compared to HS mice. Our findings reveal the protective effects of CWP against testis injury and infertility induced by exposure to HS by rescuing functional Leydig cells. Additionally, the present study has shed light on the molecular mechanisms underlying improved testicular damage following CWP treatment.

Nanocurcumin and curcumin prevent N, N'-methylenebisacrylamide-induced liver damage and promotion of hepatic cancer cell growth.

Acrylamide (AC) is an environmental contaminant with cancer-promoting and cytotoxic properties, while curcumin (Cur.) is a phytochemical with documented anticancer and cytoprotective efficacy. Nanoparticle formulations can increase the efficacy of phytochemicals, so we examined the anticancer and hepatoprotective efficacies of nanocurcumin (N.Cur). Curcumin and nanocurcumin reduced HepG2 and Huh-7 cancer cell viability and increased apoptosis in the presence and absence of AC, while AC alone promoted proliferation. Furthermore, the anticancer efficacy of nanocurcumin was greater than that of curcumin. In mice, AC greatly increased hepatic expression of CYP2E1, P53, cleaved caspase-3, and COL1A1 as well as serum alanine aminotransferase and aspartate aminotransferase activities. These effects were reversed by nanocurcumin and curcumin. Nanocurcumin also reduced the histopathology and fibrosis caused by AC, and reversed AC-induced glycogen depletion. Nanoparticle formulation can increase the anticancer and hepatoprotective efficiencies of curcumin.

The protective role of musk on salivary glands of mice exposed to chronic unpredictable mild stress.

This study assessed the impact of chronic unpredictable mild stress (CUMS) on the structure of mouse salivary glands and the role of musk in alleviating this impact. Forty male albino mice were distributed equally into four groups; control (untreated), CUMS (exposed to CUMS for 4 weeks), CUMS+fluoxetine (FLU) (exposed to CUMS then treated with FLU, CUMS+musk (exposed to CUMS then treated with musk). Behavioral changes and serum corticosterone levels were assessed at the end of the experiment. The submandibular and parotid glands were dissected out and processed for histopathological and immunohistochemical examination using antibodies against alpha smooth muscle actin (ASMA) and brain-derived neurotropic factor (BDNF). Exposure to CUMS significantly (P < 0.001) increased the serum corticosterone level and induced depression. CUMS also induced vacuolation in acinar cells along with a significant (P < 0.001) reduction of ASMA immunoexpression, indicating an effect on myoepithelial cells, and a significant (P < 0.001) increase of BDNF expression in the gland ductal system. Both FLU and musk alleviated the CUMS-induced behavioral, biochemical and histopathological changes in the salivary glands. In conclusion, musk ameliorates stress-induced structural changes in mouse salivary glands. This effect might be mediated through up-regulation of BDNF secretion by the glands.

Camel whey protein enhances lymphocyte survival by modulating the expression of survivin, bim/bax, and cytochrome C and restores heat stress-mediated pathological alteration in lymphoid organs.

OBJECTIVES: Heat stress (HS) is a catastrophic stressor that dampens immunity. The current study investigates the effect of dietary administration with camel whey protein (CWP) on apoptotic pathway caused by HS. MATERIALS AND METHODS: Forty-five male mice were divided into three groups: a control group; HS group; and HS mice that were orally supplemented with CWP (CWP-HS group). RESULTS: We found that reactive oxygen species (ROS), pro-inflammatory cytokines (IL-6), and C reactive protein (CRP) were elevated in the HS group along with a significant increase of caspase-9 and -3 and decrease of total antioxidant capacity (TAC). HS mice revealed impaired phosphorylation of Bcl-2 and Survivin, as well as increased expression of Bax, Bim and cytochrome C. Additionally, we observed an aberrant distribution of HSP-70 expressing lymphocytes in the spleen and thymus of HS mice. Moreover, histopathological examination showed alterations on the architectures of immune organs. In comparison with CWP-HS group, we found that CWP restored the levels of ROS, IL-6, TAC and CRP induced by HS. Furthermore, CWP restored the expression of Bcl-2/Bax, improved the histopathological changes in immune organs and HSP-70 distribution in the spleen and thymus. CONCLUSION: Our findings revealed the possible ameliorative role of CWP supplementation against damages induced by exposure to HS.

The protective role of quince leaf extract against the adverse impacts of ultraviolet--a radiation on some tissues of Clarias gariepinus (Burchell, 1822).

In the present study the protective role of quince leaf extract against the adverse impacts of ultraviolet radiation-A (UVA) on some tissues of Clarias gariepinus (Burchell, 1822) was considered. Fishes were classified into four groups: control, UVR-treated group (for 3days/for 3h/day), UVR-treated group (for 3days/for 3h/day) with adding 10ml of quince extract, and UVR-treated group (for 3days/for 3h/day) with adding 20ml of quince leaf extract. Blood smears and sections of the liver, and skin were processed routinely for H & E paraffin embedding technique. Some UVA-induced malformations were recorded in the red blood cells including crenated cells (Cr), Acanthocytes (Ac), tear drop-like cells (Tr) and sickle cells (Sk). Also, UVA-induced disorganization of the normal architecture of hepatic tissues with lipidosis was evident. Hypertrophy and vacuolated club cells were recorded in skin exposed to UVA. In conclusion, quince leaf extract has a valuable antioxidant protective role to prevent and/or repair the histopathological changes induced by UVA.