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.

Benefits of Chlorella vulgaris against Cadmium Chloride-Induced Hepatic and Renal Toxicities via Restoring the Cellular Redox Homeostasis and Modulating Nrf2 and NF-KB Pathways in Male Rats.

In our life scenarios, we are involuntarily exposed to many heavy metals that are well-distributed in water, food, and air and have adverse health effects on animals and humans. Cadmium (Cd) is one of the most toxic 10 chemicals reported by The World Health Organization (WHO), affecting organ structure and function. In our present study, we use one of the green microalga Chlorella vulgaris (ChV, 500 mg/kg body weight) to investigate the beneficial effects against CdCl2-induced hepato-renal toxicity (Cd, 2 mg/kg body weight for 10 days) on adult male Sprague-Dawley rats. In brief, 40 adult male rats were divided into four groups (n = 10); Control, ChV, Cd, and Cd + ChV. Cadmium alters liver and kidney architecture and disturbs the cellular signaling cascade, resulting in loss of body weight, alteration of the hematological picture, and increased ALT, AST, ALP, and urea in the blood serum. Moreover, cadmium puts hepatic and renal cells under oxidative stress due to the up-regulation of lipid peroxidation resulting in a significant increase in the IgG level as an innate immunity protection and induction of the pro-inflammatory cytokines (IL-1ß and TNF-α) that causes hepatic hemorrhage, irregular hepatocytes in the liver and focal glomeruli swelling and proximal tubular degeneration in the kidney. ChV additive to CdCl2, could organize the protein translation process via NF-kB/Nrf2 pathways to prevent oxidative damage by maintaining cellular redox homeostasis and improving the survival of and tolerance of cells against oxidative damage caused by cadmium. The present study shed light on the anti-inflammatory and antioxidative properties of Chlorella vulgaris that suppress the toxicity influence of CdCl2.

Physiological and Neurobehavioral Disturbances Induced by Al2O3 Nanoparticle Intoxication in Nile Tilapia Fish: Benefits of Dietary Chamomile Essential Oil.

Despite the usage of nanoparticles (NPs) is rapidly increasing, several experts have noted the risk of their release into ecosystems and their potential negative impacts on biological systems. However, the available studies on the neurobehavioral impacts of aluminum oxide nanoparticles (Al2O3NPs) on aquatic organisms are little. Hence, this study targeted to ascertain the harmful effects of Al2O3NPs on behavioral characteristics and genotoxic and oxidative damages in Nile tilapia fish. In addition, the beneficial role of chamomile essential oil (CEO) supplementation in reducing these effects was also investigated. In the current study, fish were distributed into 4 equal groups (n = 60 fish per group). The control group was fed a plain diet only, the CEO group received a basic diet complemented with CEO at a level of 2 mg/kg diet, the ALNP group received a basic diet and was exposed to an approximate concentration of 1/10th LC50 of ALNPs nearly 5.08 mg/L, and the combination group (ALNPs/CEO group) received a basal diet coadministered with ALNPs and CEO at the aforementioned percentages. The findings revealed that O. niloticus exhibit neurobehavioral changes along with changes in the level of GABA, monoamines in the brain tissue, and serum amino acid neurotransmitters, besides a reduction of AChE and Na+/K+-ATPase activities. In addition to brain tissue oxidative damage with upregulation of proinflammatory and stress genes, such as HSP70 and caspase-3, supplementation of CEO significantly reduced the negative impacts of ALNPs. These results showed that CEO has neuroprotective, antioxidant, genoprotective, anti-inflammatory, and antiapoptotic properties in fish that have been exposed to ALNPs. Therefore, we advise its usage as a valuable addition to fish diet.

Origanum vulgare Essential Oil Modulates the AFB1-Induced Oxidative Damages, Nephropathy, and Altered Inflammatory Responses in Growing Rabbits.

The current study was performed to investigate the toxic effects of aflatoxin B1 (AFB1) through the evaluation of kidney function tests and histopathological examination of renal tissues, targeting the therapeutic role of Marjoram (Origanum vulgare essential oil-OEO) in improving health status. Forty-eight New Zealand Whites growing rabbits (four weeks old) weighing on average 660.5 ± 2.33 g were randomly and equally distributed into four groups, each of which had four replicas of three animals as the following: Control group (only basal diet), AFB1 group (0.3 mg AFB1/kg diet), OEO group (1 g OEO/kg diet) and co-exposed group (1 g OEO/kg + 0.3 mg AF/kg diet). Our study lasted eight weeks and was completed at 12 weeks of age. The results revealed that OEO decreased the toxic effects of AFB1 in rabbit kidneys by substantially reducing the cystatin C levels in the AFB1 group. Additionally, OEO decreased oxidative stress and lipid peroxidation levels in the co-exposed group. Moreover, OEO reduced DNA damage and inflammatory response in addition to the down-regulation of stress and inflammatory cytokines-encoding genes. Besides, OEO preserved the cytoarchitecture of rabbits' kidneys treated with AFB1. In conclusion, O. vulgare essential oil supplementation ameliorated the deleterious effects of AFB1 on the rabbits' kidneys by raising antioxidant levels, decreasing inflammation, and reversing oxidative DNA damage.

Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway.

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress.

Effects of different feeding regimens with protease supplementation on growth, amino acid digestibility, economic efficiency, blood biochemical parameters, and intestinal histology in broiler chickens.

BACKGROUND: This study was conducted to estimate the impacts of using varied feeding regimens with or without protease supplementation on the growth performance, apparent amino acid ileal digestibility (AID%), economic efficiency, intestinal histology, and blood biochemical parameters of broiler chickens. Three hundred one-day-old chicks (Ross 308 broiler) were randomly allotted to a 3 × 2 factorial design. The experimental design consisted of three feeding regimens; FR1: a recommended protein SBM diet, FR2: a low-protein SBM diet, and FR3: a low-protein diet with the inclusion of 5% DDGS and 5% SFM, with or without protease supplementation (250 mg/kg). RESULTS: Increased feed intake and feed conversion ratio were observed in the FR3 treatment during the starter stage and decreased body weight and body weight gain during the grower stage. However, there was no significant effect of the different feeding regimens, protease supplementation, or interaction on the overall performance. The economic value of diets also remained unaffected by the different feeding regimens, protease supplementation, or interaction. Protease supplementation resulted in lowering the AID% of tryptophan and leucine. Reduced AID% of methionine was evident in the FR2 + VE and FR3 - VE treatments. Histological findings substantiated the FR3 treatment mediated a decrease in the duodenal and jejunal villous height (VH), jejunal villous width (VW), and ileal VW, whereas, increase in the ileal crypt depth (CD). The FR2 + VE treatment reduced the VH:CD ratio in the duodenum. The duodenal CD and the jejunal goblet cell count were reduced as a consequence of protease supplementation. The FR3 + VE treatment documented a rise in duodenal CD, while an increase in the jejunal goblet cell count was observed in the FR3 - VE treatment. The FR3 treatment enhanced the IgM serum levels compared to the FR1 and FR2 treatments. IgM serum levels were also elevated following protease supplementation. FR3 + VE treatment increased IgM serum levels. The highest serum ALP was found in the FR3 treatment, whereas the lowest level was obtained in the FR2 treatment. CONCLUSION: Low-protein SBM-based diets could be used without affecting the birds' growth. Altered morphometric measures of the intestine and increased IgM and ALP levels indicated the low-protein SBM/DDGS-SFM diet-induced damage of the intestinal histoarchitecture and immune system of birds. These different diets and protease supplementation failed to affect economic efficiency positively.

Thymol alleviates imidacloprid-induced testicular toxicity by modulating oxidative stress and expression of steroidogenesis and apoptosis-related genes in adult male rats.

The present work was designed to assess the potential ameliorative effect of thymol on the testicular toxicity caused by imidacloprid (IMI) in adult male rats. Forty adult male rats were allocated into four groups; control group was given corn oil, thymol-treated group (30 mg/kg b.wt), IMI-treated group (22.5 mg/kg b.wt), and IMI + thymol-treated group. All administrations were done by gavage every day for duration of 56 days. As a result, the IMI exposure caused a significant decline in the body weight change, reproductive organ weights, sperm functional parameters, and serum level of testosterone, widespread histological alterations, and apoptosis in the testis. Additionally, the IMI-treated rats exhibited a remarkable increment in the serum levels of follicle stimulating hormone and luteinizing hormone. Also, IMI induced testicular oxidative stress, as indicated by elevated malondialdehyde (MDA) levels and a marked decline in the activity of antioxidant enzymes and reduced glutathione (GSH), and total antioxidant capacity (TAC) levels. Moreover, IMI treatment significantly downregulated the mRNA expression of steroidogenic genes and proliferating cell nuclear antigen (PCNA) immunoexpression in the testicular tissue. However, thymol co-administration significantly mitigated the IMI-induced toxic effects. Our findings suggested that IMI acts as a male reproductive toxicant in rats and thymol could be a potential therapeutic option for IMI reprotoxic impacts.

The protective efficacy of vitamin E and cod liver oil against cisplatin-induced acute kidney injury in rats.

Cisplatin (CP) is a highly effective chemotherapeutic agent against neoplasms, but its clinical utility is limited due to the side effects of its dose-dependent nephrotoxicity. Vitamin E (Vit E) and cod liver oil (CLO) are natural substances with chemoprotective effects. The present study was conducted to evaluate the protective effects of Vit E and/or CLO for CP-induced acute kidney injury (AKI) in rats. This study involved 40 mature male Wistar albino rats that were equally allocated into eight groups: Veh, Vit E, CLO, Vit E + CLO, CP, Vit E + CP, CLO + CP, and Vit E + CLO + CP. The co-administration of Vit E and CLO significantly ameliorated CP-induced elevations in serum creatinine (Cr), blood urea nitrogen (BUN), interleukin 1 beta (IL-1ß), and interleukin- 6 (IL-6). Further, rats that received Vit E and/or CLO showed significant decrease in malondialdehyde (MDA) and increases in superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels in renal tissues, compared to CP-intoxicated rats. Additionally, the treatment restored the normal histological architecture (except for few cast formations) and upregulated the immunostaining area% of aquaporin 3 (AQP3) and downregulated the immunostaining area% of Bcl2 associated X protein (BAX) and inducible nitric oxide synthase (iNOS). The observed effects were stronger in the combination treatment group. The obtained data revealed that Vit E and CLO co-administration protects against the CP-induced AKI more than monotherapy with Vit E or CLO.

Neurobehavioral, apoptotic, and DNA damaging effects of sub-chronic profenofos exposure on the brain tissue of Cyprinus carpio L.: Antagonistic role of Geranium essential oil.

Currently, the contamination of water with different insecticides like profenofos (PFF) is a critical concern in the aquatic ecosystem. There are limited studies available on the negative impacts of PFF on common carp fish (Cyprinus carpio L.). Therefore, the existing study was designed to investigate the effect of PFF exposure (1/10 of the 96 h-LC50) on the neurobehavior, growth performance, chemical composition, oxidative status, DNA damage, apoptotic status and histological indices of the brain and gill tissues. In addition, this study seeks to detect the ability of geranium essential oil (GEO) dietary supplementation to mitigate the negative impacts of PFF. Accordingly, a total of 120 healthy fish were divided into four groups: the control group, fed on basal diet only; the other groups were fed on a basal diet supplemented with 400 mg kg-1 GEO, basal diet and PFF in water (PFF group), and supplemented diet with GEO and PFF in water (GEO + PFF), respectively, for 60 days. The results showed that PFF significantly reduced fish growth performance, crude protein, and lipid contents. It caused several behavioral alterations including spiral movement, decreased activeness, and changes in feeding behavior. Moreover, PFF increased the DNA tail length, tail moment, and the level of 8-hydroxy-2'-deoxyguanosine. Histologically, PFF induced a wide array of circulatory, inflammatory, regressive and progressive alterations in the brain and gill tissues. PFF significantly downregulated Bcl-2 and upregulated caspase-3 immuno-expression in both organs. Further, it considerably depleted the antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. The GEO supplementation did not reach the respective control values but markedly improved most of the behavioral, physical, biochemical, oxidative, apoptotic, and inflammatory markers, altered by PFF exposure. It also protected the gill and brain tissues from the branchial and encephalopathic effects of PFF. These findings suggest that GEO dietary supplements could be advantageous for mitigating PFF negative impacts and presenting a promising feed additive for common carp in aquaculture.

Curcumin mitigates mancozeb-induced hepatotoxicity and genotoxicity in rats.

Mancozeb (MZ) is a widely used ethylene-bis-dithiocarbamate fungicide in agriculture causing hepatoxic and genotoxic effects in rats. Curcumin (CUR) has various pharmacological effects including antioxidant and anti-inflammatory properties. This study investigated the efficacy of CUR in mitigating MZ-induced hepatotoxicity and genotoxicity in rats. Twenty-four male rats were divided into four equal groups; group I (control) was given carboxymethyl cellulose, group II was orally administered CUR (100 mg/kg b.wt), group III was gavaged with MZ (750 mg/kg b.wt), and group IV was co-treated with MZ and CUR at the same doses daily for 10 weeks. As a result, the concurrent treatment with CUR and MZ minimized the increased levels of liver function markers in serum, lipid peroxidation, pro-inflammatory mediators and DNA damage parameters in liver. In addition, CUR administration improved the depleted markers of hepatic antioxidant status in MZ-treated rats. Moreover, CUR protected the liver against the histological alterations elicited by MZ exposure and also, reduced the immunopositive reactivity of pro-apoptotic p53 in cytoplasm of hepatocytes. The present findings suggest that CUR exerts a significant protective effect against MZ-induced hepatotoxicity and genotoxicity.

Amelioration of fenitrothion induced oxidative DNA damage and inactivation of caspase-3 in the brain and spleen tissues of male rats by N-acetylcysteine.

N-acetylcysteine (NAC) has largely been used as an effective chemo- protective agent owing to their beneficial effect in restoring several physiological parameters and relieving oxidative stress. Interestingly, it has been suggested that NAC mechanisms of action extend beyond being a precursor to the antioxidant glutathione and that they may involve several neurotropic and inflammatory pathways. Exposure to fenitrothion, an organophosphorus insecticide, promotes oxidative stress and induces several deleterious changes in the immune response and various tissues including cerebrum and spleen. The main objective of our study was to investigate ameliorative efficacy of N-acetylcysteine for immunological and neurological alterations and oxidative DNA damage induced by fenitrothion toxicity in cerebrum and spleen tissues of male rats. Our results revealed that oral exposure to fenitrothion for 30 days caused a reduction in the erythrocyte count in addition to leukocytosis, lymphocytosis, and neutrophilia. Also, this route of administration increased the serum levels of LDH, TNF-α, and IL-2 with reduction in serum immunoglobulins (IgG & IgM) concentrations. Furthermore, a significant downregulation in the antioxidant markers (GSH & SOD) with an elevation of free radical (MDA) levels were noticed. Regarding the brain, fenitrothion administration inhibited AchE activity and increased brain GABA, serotonin and dopamine levels. Moreover, it induced an elevation in oxidative DNA damage indicated by 8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine co-treatment restored the normal physiological tone in most of these parameters. Immunostaining for GFAP and Caspase-3 markers in the brain and spleen tissues were increased respectively. In conclusion, N-acetylcysteine supplementation has an ameliorative effect against immunotoxic, neurotoxic and oxidative DNA damage induced by fenitrothion exposure.