Nicotine exacerbates liver damage in a mice model of Ehrlich ascites carcinoma through shifting SOD/NF-κB/caspase-3 pathways: ameliorating role of Chlorella vulgaris.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco's life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 106 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1, SOD2, CAT, GPX1, and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Dietary Curcumin Modulating Effect on Performance, Antioxidant Status, and Immune-Related Response of Broiler Chickens Exposed to Imidacloprid Insecticide.

Birds appear to be especially vulnerable to adverse impacts from insecticides. This is especially true for imidacloprid (IMI), which is considered the most toxic to avian species. Recently, prospective studies aimed at including natural alternative products to alleviate the toxic impact that comes from insecticides have been increased. Focusing on herbal growth promoters and antioxidative medicament for the poultry industry, this ongoing experiment was conducted to examine the curcumin role (CUR) in mitigating IMI-prompted detrimental effects on broilers' performance, immunity, and antioxidant status. A total number of one hundred and fifty commercial meat-type Ross 308 broilers chicks (one-day-old) were randomly allocated into equal five groups (30 chicks/group and 10 birds/replicate). The first group (C) was the control; the second group (CUR) was fed a diet containing CUR at the level of 450 mg/kg; the third group (IMI) was fed control diet for 14 days and then was fed a diet containing IMI at the level of 50 mg/kg; the fourth group (CUR+IMI co-treated) was fed a diet containing CUR+IMI; and the fifth group (CUR+IMI pro/co-treated) was fed a diet containing CUR for 14 days as protective and then a diet containing CUR+IMI for the rest of the trial. CUR supplementation either in the (CUR pro/co-treated) or (CUR co-treated) groups significantly (p < 0.05) improved final body weight and total body weight gain while decreasing the total feed intake and feed conversion ratio when compared to the IMI-exposed and non-treated birds. CUR induced a significant (p < 0.05) enhancement in hematological indices, phagocytosis %, phagocytic index, intracellular killing capacity, total proteins, globulin, liver function enzymes, lysozyme activity, and immunoglobulin-G levels compared to IMI-exposed and non-treated birds. In addition, dietary supplementation of CUR significantly (p < 0.05) modulated oxidative stress-related biomarkers in splenic tissues (total antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase) and decreased malondialdehyde levels (p < 0.05) when compared to IMI-exposed and non-treated birds. CUR significantly down-regulated mRNA levels expression of IL-1ß, TNF-α, and TLR4 and up-regulated IL-10 mRNA expression levels in spleens of birds when compared to those exposed to IMI-and non-treated. Finally, our results provided new insight into IMI-induced immuno-toxicity in broiler chickens. Furthermore, for the first time, our study informed that CUR can cause an in vivo protective effect against IMI toxicity, principally as a protective and/or as concurrent supplementation during the exposure to IMI toxicity.

Apitoxin alleviates methyl mercury-induced peripheral neurotoxicity in male rats by regulating dorsal root ganglia neuronal degeneration and oxidative stress.

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats.

Protective prospects of eco-friendly synthesized selenium nanoparticles using Moringa oleifera or Moringa oleifera leaf extract against melamine induced nephrotoxicity in male rats.

Nanotechnology is used in a wide range of applications, including medical therapies that precisely target disease prevention and treatment. The current study aimed firstly, to synthesize selenium nanoparticles (SeNPs) in an eco-friendly manner using Moringa oleifera leaf extract (MOLE). Secondly, to compare the protective effects of green-synthesized MOLE-SeNPs conjugate and MOLE ethanolic extract as remedies for melamine (MEL) induced nephrotoxicity in male rats. One hundred and five male Sprague Dawley rats were divided into seven groups (n = 15), including 1st control, 2nd MOLE (800 mg/kg BW), 3rd SeNPs (0.5 mg/kg BW), 4th MOLE-SeNPs (200 µg/kg BW), 5th MEL (700 mg/kg BW), 6th MEL+MOLE, and 7th MEL+MOLE SeNPs. All groups were orally gavaged day after day for 28 days. SeNPs and the colloidal SeNPs were characterized by TEM, SEM, and DLS particle size. SeNPs showed an absorption peak at a wavelength of 530 nm, spherical shape, and an average size between 3.2 and 20 nm. Colloidal SeNPs absorption spectra were recorded between 400 and 700 nm with an average size of 3.3-17 nm. MEL-induced nephropathic alterations represented by a significant increase in serum creatinine, urea, blood urea nitrogen (BUN), renal TNFα, oxidative stress-related indices, and altered the relative mRNA expression of apoptosis-related genes Bax, Caspase-3, Bcl2, Fas, and FasL. MEL-induced array of nephrotoxic morphological changes, and up-regulated immune-expression of proliferating cell nuclear antigen (PCNA) and proliferation-associated nuclear antigen Ki-67. Administration of MOLE or MOLE-SeNPs significantly reversed MEL-induced renal function impairments, oxidative stress, histological alterations, modulation in the relative mRNA expression of apoptosis-related genes, and the immune-expression of renal PCNA and Ki-67. Conclusively, the green-synthesized MOLE-SeNPs and MOLE display nephron-protective properties against MEL-induced murine nephropathy. This study is the first to report these effects which were more pronounced in the MOLE group than the green biosynthesized MOLE-SeNPs conjugate group.

Bee venom Apis mellifera lamarckii rescues blood brain barrier damage and neurobehavioral changes induced by methyl mercury via regulating tight junction proteins expression in rat cerebellum.

The objective of the current study is to investigate the protective effect of Egyptian bee venom (BV) against methyl mercury chloride (MMC) induced blood-brain barrier (BBB) damage and neurobehavioral changes. Eighty male Sprague-Dawley rats were randomly grouped into 1st control (C), 2nd BV (0.5 mg/kg S/C for14 days), 3rd MMC (6.7 mg/kg orally/14 days), and 4th MMC + BV group. MMC exposure significantly altered rat cognitive behavior, auditory startle habituation, and swimming performance, increased the exploratory, grooming, and stereotypic behavior. MMC significantly impaired BBB integrity via induction of inflammation, oxidative stress, and down-regulation of tight junction proteins genes (TJPs) mRNA expression levels: Occludin (OCC), Claudins-5 (CLDN5), Zonula occludens-1 (ZO-1), while up-regulated the transforming growth factor-beta (TGF-ß) mRNA expression levels. MMC revealed a significantly higher percentage of IgG positive area ratio, a higher index ratio of Iba1, Sox10, and ss-DNA, while index ratio of CD31, neurofilament, and pan neuron showed a significant reduction. Administration of BV significantly regulates the MMC altered behavioral responses, TJPs relative mRNA expression, and the immune-expression markers for specific neural cell types. It could be concluded for the first time that BV retains a promising in vivo protection against MMC-induced BBB dysfunction and neurobehavioral toxicity.

Dietary exposure to methyl mercury chloride induces alterations in hematology, biochemical parameters, and mRNA expression of antioxidant enzymes and metallothionein in Nile tilapia.

Methyl mercury chloride "MMC" (CH3ClHg) is an ubiquitous environmental toxicant that causes a variety of adverse effects. In the present study, we investigated the effects of sub-chronic toxicity of MMC on Nile tilapia (Oreochromis niloticus) through the evaluation of growth performance and hematological, biochemical, and oxidative stress biomarkers. From 150 healthy fish, five equally sized treatment groups were created: a control (CT) group fed with a basal diet and four MMC treatment groups exposed to 0.5, 1, 1.5, and 2 mg of MMC per kg of basal diet for 60 days. MMC exposure significantly reduced the growth performance and survival of O. niloticus and decreased red blood cell count and hemoglobin concentration. Treated fish exhibited normocytic normochromic anemia in addition to leucopenia, lymphopenia, granulocytopenia, and monocytopenia. Moreover, MMC exposure significantly affected liver function, including a reduction in the total protein levels while increasing cholesterol and triglyceride levels. It also markedly increased the production of stress biomarkers such as glucose and cortisol levels. Furthermore, MMC significantly elevated the levels of hepatic enzymes, induced tissue damage, and caused inflammation, as indicated by the upregulation of mRNA expression of hepatic metallothionein. Finally, MMC exposure induced oxidative stress by altering the antioxidant status of the liver and downregulating the mRNA expression of superoxide dismutase, glutathione peroxidase, and glutathione S-reductase. In conclusion, MMC toxicity induced hematological and biochemical alterations, leading to an enhanced state of oxidative stress in O. niloticus.

Neurobehavioral and immune-toxic impairments induced by organic methyl mercury dietary exposure in Nile tilapia Oreochromis niloticus.

Although substantial knowledge of mercury toxicity in fish has been assembled; until now, studies investigating the toxic impacts in Nile tilapia (Oreochromis niloticus) following dietary exposure to organic methyl mercury (MeHg) are less prolific. Accordingly, the current study aimed to evaluate the impacts of MeHg on neurobehavioral and immune integrity in Nile tilapia after dietary exposure. Two hundred and twenty-five juvenile Nile tilapia (19.99 ± 0.33 g) were allocated into five groups in triplicates (15 fish/replicate). G1, G2, G3, G4, and G5. O. niloticus were fed corresponding basal diets containing 0, 0.5, 1, 1.5, and 2 mg/kg diet MeHg chloride (MeHgCl) daily for 30 days, zero value represented the control G1 group. The results showed that MeHg induced significant alterations in O. niloticus behavior, the swimming behavior was significantly decreased, while scratching, biting, and fin tugging behaviors were significantly augmented. Moreover; chasing, mouth pushing, and butting behaviors were significantly increased in all the exposed groups. MeHg significantly decreased brain acetylcholine esterase (AChE) and serum immunoglobulin M (IgM) levels in all the exposed groups. Meanwhile, serum levels of lysozyme (LYZ), nitric oxide (NO), superoxide dismutase (SOD) malondialdehyde (MDA), protein carbonyl (PCO), and 8 hydroxy 2 deoxyguanosine (8OH2dG) were significantly elevated in all the exposed groups except for serum reduced glutathione (GSH) content was significantly decreased implying oxidative stress (OS), lipid peroxidation (LPO), protein, DNA damage and impaired immune response of the exposed tilapia. MeHg significantly altered transcriptional expression of immune-related genes including (TNF-α, IL-1ß, and IL-8, and IL-10) in all the exposed groups. From the obtained outcomes, the present research is the premier to investigate that dietary MeHg exposure in O. niloticus significantly induced neurobehavioral and immune defense impairments in a dose-related manner. This study exhibits that dietary MeHg may pose a potential threat to the O. niloticus populations.

The palliative effect of camel milk on hepatic CYP1A1 gene expression and DNA damage induced by fenpropathrin oral intoxication in male rats.

The present study investigated the alleviating role of camel milk (CM) in the mitigation of fenpropathrin (FNP) type II pyrethroid induced oxidative stress, alterations of hepatic (CYP1A1) mRNA expression pattern, and DNA damage using the alkaline comet assay (SCGE) in male rats. Sixty male Sprague-Dawley rats were separated into six groups (n = 10): 1st control (C), 2nd corn oil (CO), 3rd (CM): gavaged CM 2ml/rat, 4th (FNP): gavaged FNP 7.09 mg/kg body weight (BW), 5th (FNP pro/co-treated): gavaged CM firstly for 15 days, then CM + FNP by the same mentioned doses and route, 6th (FNP + CM co-treated): gavaged FNP firstly followed by CM by the same mentioned doses and route. Rats were orally gavaged three times per week, day after day for 60 days. FNP exposure significantly reduced serum glutathione (GSH) levels, but significantly increased serum levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), protein carbonyl (PCO), and 8hydroxy2deoxyguanosine (8OH2dG). Additionally, FNP exposure significantly up-regulated the mRNA expression levels of hepatic CYP1A1 and increased the SCGE indices in whole blood, liver, and spleen tissues of exposed male rats. Administration of CM significantly regulated the FNP induced oxidative stress, reduced hepatic CYP1A1 mRNA expression levels and values of comet assay indices particularly in the (CM + FNP pro/co-treated) group compared to the (FNP + CM co-treated) group. In conclusion, our results indicate, for the first time, that FNP retains an in vivo genotoxic potential at a dose of (1/10 LD50) and up-regulated hepatic CYP1A1 mRNA expression in male rats. Additionally, CM supplements may improve the genotoxic outcomes, oxidative stress, and altered CYP1A1 mRNA expression induced by FNP particularly in the pro/concurrent-treatment compared to the concurrent treatment alone.

Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway to Restore Kidney Tissue from Cobalt-Mediated Oxidative Injury and Inflammation in Rats.

This study aimed to describe the protective efficacy of Moringa oleifera ethanolic extract (MOEE) against the impact of cobalt chloride (CoCl2) exposure on the rat's kidney. Fifty male rats were assigned to five equal groups: a control group, a MOEE-administered group (400 mg/kg body weight (bw), daily via gastric tube), a CoCl2-intoxicated group (300 mg/L, daily in drinking water), a protective group, and a therapeutic co-administered group that received MOEE prior to or following and concurrently with CoCl2, respectively. The antioxidant status indices (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), oxidative stress markers (hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and malondialdehyde (MDA)), and inflammatory response markers (nitric oxide (NO), tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and C-reactive protein (CRP)) were evaluated. The expression profiles of pro-inflammatory cytokines (nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6)) were also measured by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that CoCl2 exposure was associated with significant elevations of oxidative stress and inflammatory indices with reductions in the endogenous tissue antioxidants' concentrations. Moreover, CoCl2 enhanced the activity of the NF-κB inflammatory-signaling pathway that plays a role in the associated inflammation of the kidney. MOEE ameliorated CoCl2-induced renal oxidative damage and inflammatory injury with the suppression of the mRNA expression pattern of pro-inflammatory cytokine-encoding genes. MOEE is more effective when it is administered with CoCl2 exposure as a prophylactic regimen. In conclusion, MOEE administration exhibited protective effects in counteracting CoCl2-induced renal injury in rats.

Dose-related impacts of imidacloprid oral intoxication on brain and liver of rock pigeon (Columba livia domestica), residues analysis in different organs.

Available data regarding Imidacloprid (IMI) insecticide hazards to birds are still being scare. Our study aimed to investigate toxic impacts of IMI oral gavage by different dose levels on the brain and liver of Rock pigeon (Columba livia domestica). Forty mature male birds were divided equally into four groups. A control group (C) was orally dosed Mazola corn oil and other three groups; the low dose (LD), the medium dose (MD), and the high dose (HD) groups were orally dosed IMI in Mazola corn oil by three dose levels corresponding to 1/15th, 1/10th, 1/5th IMI oral LD50 respectively. IMI exposure induced a significant decrease in serum levels of glutathione (GSH), superoxide dismutase (SOD) enzyme activity. On the other hand; malondialdehyde (MDA) levels were elevated. The levels of serum total protein, albumin, globulin, and A/G ratio showed a non-significant changes in all IMI dosed groups except levels of total protein in the HD IMI dosed group showed a significant decrease compared to the C group. Serum levels of alanine aminotransferase (ALT), lactate dehydrogenase (LDH), uric acid, plasma tumor necrosis factor α (TNFα) and plasma acetylcholinesterase (AChEs) enzyme activities showed a significant dose related increase in all IMI exposed groups compared to the C group; except the levels of ALT, LDH, and uric acid showed a non significant decrease in the LD IMI dosed group only. Residues of IMI were detected in the pectoral muscles, liver, brain, and kidney of all dosed rock pigeon. Moreover; pectoral muscles were the highest tissue for IMI residues detection. This is the first study reports accumulation of IMI in tissues other than crop, liver, and kidney of rock pigeon including brain and muscles. Moreover, the examined brain and liver tissues of all IMI dosed groups showed dosed related alterations in their structural and ultra-structural morphology. It is concluded that IMI oral administration to pigeon induced oxidative stress and detrimental effects in brain and liver of exposed pigeons. Additionally; IMI bio-accumulated in different organs being muscles is the highest tissues for IMI residues, thus monitoring of IMI residues in food is very essential.

Ascorbic acid protects male rat brain from oral potassium dichromate-induced oxdative DNA damage and apoptotic changes: the expression patterns of caspase-3, P 53, Bax, and Bcl-2 genes.

Our study designed to study the potential of potassium dichromate (K2Cr2O7) oral exposure to induce damage in male rat brain and to compare the possible protective role of vitamin C (VC) either pre and/or concurrent supply against (K2Cr2O7) induced changes. Thirty male rats were divided into five groups. First control group received distilled water (C), second received 120 mg/kg b.wt (VC), third received 25 mg/kg b.wt K2Cr2O7 (Cr), fourth group received VC together with K2Cr2O7 by the same former doses (VC + Cr), and the fifth group received the same oral doses of VC 2 weeks prior to and along with K2Cr2O7 for 6 weeks (VC + Cr pro/co treated). The obtained results revealed that K2Cr2O7 induced a significant decrease in cholinergic activity, glutathione reductase GR activity, reduced glutathione content GSH and ATP levels. Furthermore, K2Cr2O7 induced a significant increase in oxidative DNA damage indicated by 8-hydroxy 2'-deoxyguanosine (8OH2'dG) and formation of apoptotic DNA ladders, significant increase in malondialdehyde (MDA), protein carbonyl, and lactate dehydrogenase enzyme. Increased mRNA expression of pro-apoptotic genes, including caspase-3, p53, and Bax, unlike Bcl-2 expression, was decreased. K2Cr2O7 increased caspase-3 and decreased Bcl-2 immuno-labeling. VC supply noticeably ameliorates K2Cr2O7-induced changes which were more significantly in VC pro and concurrent supplement rather than VC concurrent supply only. Finally, it is concluded that K2Cr2O7 oral administration induced oxidative apoptotic changes in rat brain and confirms the usefulness of VC pre and concurrent supply for the amelioration of K2Cr2O7-induced events more significantly than VC concurrent supply only.