Thymol's modulation of cellular macromolecules, oxidative stress, DNA damage, and NF-kB/caspase-3 signaling in the liver of imidacloprid-exposed rats.

We evaluated whether thymol (THY) (30 mg/kg b.wt) could relieve the adverse effects of the neonicotinoid insecticide imidacloprid (IMD) (22.5 mg/kg b.wt) on the liver in a 56-day oral experiment and the probable underlying mechanisms. THY significantly suppressed the IMD-associated increase in hepatic enzyme leakage. Besides, the IMD-induced dyslipidemia was considerably corrected by THY. Moreover, THY significantly repressed the IMD-induced hepatic oxidative stress, lipid peroxidation, DNA damage, and inflammation. Of note, the Feulgen, mercuric bromophenol blue, and PAS-stained hepatic tissue sections analysis declared that treatment with THY largely rescued the IMD-induced depletion of the DNA, total proteins, and polysaccharides. Moreover, THY treatment did not affect the NF-kB p65 immunoexpression but markedly downregulated the Caspase-3 in the hepatocytes of the THY+IMD-treated group than the IMD-treated group. Conclusively, THY could efficiently protect against IMD-induced hepatotoxicity, probably through protecting cellular macromolecules and antioxidant, antiapoptotic, and anti-inflammatory activities.

Exploring cardiac impact of oral nicotine exposure in a transplantable Neoplasm Mice Model: Insights from biochemical analysis, morphometry, and molecular docking: Chlorella vulgaris green algae support.

Nicotine-induced cardiac tissue damage is a concern for cancer patients, but the exact pathogenesis from nicotine oral exposure is unclear. This study was designed to investigate the impact of nicotine and Chlorella vulgaris (Ch. V) on cardiac glutathione homeostasis, inflammatory response, cardiac damage markers, apoptotic proteins and histopathological findings in an experimentally transplantable neoplasm mouse model (Ehrlich ascites carcinoma; EAC). In the in-vivo experiment, the female Swiss mice were divided into four groups: control, Ch.V (100 mg/kg), Nicotine (100 µg/ml/kg), and a combination group ( Nocotine+ Ch.V) for 40 days. Furthermore, in this study,the effects of C. vulgaris components on caspase-3, TNF-α, and IL-1ß activity were explored using Molecular Operating Environment (MOE) docking software to ensure its ability to counteract the toxic effects of nicotine. The results indicated that nicotine has induced significant (P < 0.001) cardiopathic alterations in EAC-bearing mice with changes in cardiac tissue enzymes. C. Vulgaris attenuated the nicotine-induced cardiac glutathione inhibition, suppressed the inflammatory response, exerted antiapoptotic effects, mitigated myocardial injury biomarkers, and repaired cellular and tissue damage. Moreover, the molecular docking results revealed the ability of C. vulgaris to bind with interleukin-1 receptor type 1 (IL1R1) and tumor necrosis factor receptor superfamily member 1 A (TNFRSF1A) in the mice tissues, ameliorating apoptosis and inflammatory processes associated with nicotine-induced cardiotoxicity. This study provides a model for understanding nicotine-induced myocardial injury during experimentally transplantable neoplasm. It highlights C. vulgaris as a beneficial food supplement for cancer patients exposed to nicotine orally.

Thymol abates the detrimental impacts of imidacloprid on rat brains by lessening oxidative damage and apoptotic and inflammatory reactions.

Imidacloprid (IMID) is one of the most widely used neonicotinoid insecticides globally and, consequently, a probable widespread environmental contaminant. The potential neurotoxic effects of IMID have been previously reported. This study aimed to investigate the possible beneficial effect of thymol (TML) in relieving IMID-induced harmful effects on the brain of male Sprague-Dawley rats. For this aim, four groups (10 rats/group) were orally administered corn oil, TML (30 mg/kg b.wt), IMID (22.5 mg/kg b.wt), or TML + IMID for 56 days. The brain tissues were biochemically, histopathologically, and immunohistochemically evaluated. The results displayed that TML significantly restored the IMID-induced depletion of the total antioxidant capacity of the brain tissues. At the same time, the IMID-associated increased levels of lipid peroxidation in terms of malondialdehyde content were markedly suppressed in the TML + IMID group. Also, TML oral dosing markedly reduced the release of inflammatory elements, including nitric oxide and myeloperoxidase, resulting from IMID exposure. Furthermore, the IMID-induced decrease in gamma-aminobutyric acid but the increase in acetylcholinesterase was considerably reversed by TML oral dosing. Additionally, TML oral administration significantly counteracted the IMID-induced brainepatic DNA damage, as revealed by the comet assay. Besides, a significant downregulatibrainepatic Caspase-3 was evident in the TML + IMID group compared to the IMID group. However, TML oral dosing has not significantly altered the IMID-induced nuclear factor (NF-κB p65) increase. Therefore, TML could be a protective agent against IMID-induced detrimental impacts on brain tissue, possibly through its antioxidant, antiapoptotic, and anti-inflammatory activities.

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.

Scrutinizing pathways of nicotine effect on renal Alpha-7 nicotinic acetylcholine receptor and Mitogen-activated protein kinase (MAPK) expression in Ehrlich ascites carcinoma-bearing mice: Role of Chlorella vulgaris.

Nicotine is one of several physiologically stable and active chemicals found in tobacco. The mechanism through which nicotine causes kidney damage is still obscure. As a result, the goal of this research was to investigate how oral nicotine intake can lead to kidney damage. Naturaly occurring superfood green algae are immense supplements help us using extra chemicals during cancer prevalence if the patient is exposed to nicotine. Hence, the mitigating role of Chlorella vulgaris extract (CVE) against nicotine-nephrotoxic impact in Ehrlich ascites carcinoma (EAC)-bearing mice was studied. For this purpose, four groups of Swiss female mice were assigned, nicotine group (NIC) (100 µg/ml/kg), CVE group (100 mg/kg), CVE + Nicotine, and a control group. Renal dysfunction was evaluated by estimating serum biomarkers ofrenal damage. The expression pattern of Nf-KB, MAPK, P53, and α7-nAchR, lipid peroxidation biomarker, and antioxidant enzyme activities were evaluated in kidney tissue. Also, micro-morphometric examination and apoptosis immunohistochemical reactivity of kidney tissue were applied. The obtained results indicated up-regulation of all estimated genes and oxidative stress. Moreover, a significant (P < 0.05) increment in the apoptotic marker Caspase-3 and declined BCL-2 proteins were recorded. In serum, a significant (P < 0.05) elevation of urea, creatinine, TNF-α, IL-1ß, and Kim-1 were evident. Histological investigation reinforced the aforementioned data, revealing structural changes involving the tubules, glomeruli, and interstitium of mice kidneys. CVE may be a strong contender for protecting renal tissue damage since it reduces renal tissue injury and oxidative stress. Cancer patients who regularly use nicotine through direct smoking or second-hand exposure can benefit from CVE usage as a dietary supplement.

Sustained Functioning Impairments and Oxidative Stress with Neurobehavioral Dysfunction Associated with Oral Nicotine Exposure in the Brain of a Murine Model of Ehrlich Ascites Carcinoma: Modifying the Antioxidant Role of Chlorella vulgaris.

Background: This study provides a model for studying the mechanism(s) responsible for the nervous tissue damage and misfunctioning that occurred due to oral nicotine exposure, considered a stress factor, during the presence of Ehrlich ascites carcinoma bearing in the mouse model (EAC). The mitigating role of Chlorella vulgaris (CV) against nicotine-induced brain damage was evaluated. Methods: Eighty Swiss female mice were classified into four groups, these were the control, the CV group, the nicotine group(100 µg/kg), and the combination group. Oxidant/antioxidant status, proinflammatory cytokines levels, DNA damage, quantitative microscopical lesions, and Caspase 3, Bcl-2 proteins were assessed in the current study. Levels of dopamine (DA) and gamma-aminobutyric acid (GABA) were also evaluated. Results: Nicotine was found to cause pronounced neurobehavioral alterations, increase the mortalities oxidative stress DNA damage, and augment the inflammatory response in brain tissue alongside the microstructural alteration. The administration of CV with nicotine in EAC-bearing mice rescued the detrimental effects of nicotine. Conclusions: CV aids in reducing the harmful effects of nicotine and returns the conditions caused by nicotine to near-control levels. Thus, we are in favor of giving it to cancer patients who are taking daily dosages of nicotine even by smoking cigarettes or being exposed to second-hand smoke.

Early postmortem biochemical, histological, and immunohistochemical alterations in skeletal muscles of rats exposed to boldenone undecylenate: Forensic implication.

This study investigated the biochemical and histopathological alterations along with the immunoexpression pattern of heat shock protein 27 (Hsp27) within 6 h postmortem (PM) in skeletal muscle of boldenone (BOL)-treated rats. Forty-eight male rats were divided into two groups; a control group received sesame oil (0.25 mL/kg bwt), and BOL group received 5 mg/kg bwt BOL. Both treatments were intramuscularly injected once a week for eight weeks. Rats were euthanized by cervical dislocation, and the skeletal muscle specimens were collected at zero-time, 2, 4, and 6 h PM for biochemical and histopathological evaluations. The results revealed that BOL treatment significantly increased pH, MDA, ATP, ADP, glycogen, and hydroxyproline values. Still, it decreased the GPX, GST, and lactic acid levels, and Hsp27 immunoexpression compared to the control group. With increasing postmortem interval (PMI), whether control or BOL-treated, a significant reduction in pH value, markers of muscular antioxidant status, ATP, ADP, glycogen, hydroxyproline levels, as well as Hsp27 immunoexpression but a significant increase in lipid peroxidation and lactic acid content were recorded. Of note, the interaction between BOL treatment and PMI had a significant effect on ATP, ADP, lactic acid, hydroxyproline, GST, MDA, and TAC levels. Conclusively, these findings signify BOL exposure's modifying effect on the energy content, oxidative status, and histological architecture of skeletal muscles in the early PMI that reflected in delaying the onset of rigor mortis. For forensic practitioners, these findings should be highly considered at estimating PMI in athletic, AAS-treated patients, and fattening animals.

Boldenone undecylenate disrupts the immune system and induces autoimmune clinical hypothyroidism in rats: Vitamin C ameliorative effects.

The present study was designed to evaluate the effects of boldenone undecylenate (BL) abuse alone and in combination with vitamin C (VC) on the immune responses and thyroid structure and function in rats. Thirty adult male Wistar rats were randomly divided into five equal groups and were subjected to various treatment regimens for eight weeks as follows: control group, vehicle control group, VC group orally received VC (120 mg/Kg BW/day), BL-treated group intramuscularly injected with BL (5 mg/kg BW, once/week), and BL+VC group received BL and VC. At the end of this experiment, blood and tissue samples (thyroid, thymus, and spleen) were subjected to hematological evaluation, biochemical analysis, histopathological, and immunohistochemical examinations. In comparison to controls, BL significantly increased the levels of serum proinflammatory interleukins (IL-1 ß and IL-6), immunoglobulins (IgG and IgM), and complement 3 but reduced anti-inflammatory interleukin-10, lysosome, and nitric oxide. Besides, altered platelet count and leukogram were evident in BL-injected rats. BL notably disturbed thyroid profile as revealed by a significant increase of thyroid-stimulating hormone and thyroid peroxidase antibody. In contrast, both total and free forms of thyroid hormones (tri-iodothyronine and thyroxine), thyroglobulin, and thyroid peroxidase, were significantly decreased. Moreover, BL caused histopathological changes in the thyroid, thymus, and spleen tissues.CD4+ immuno-expression was reduced, but CD8+ immunolabelling was increased in both spleen and thymus. The daily dosing of VC to BL-exposed rats significantly corrected most of the deviations in immune parameters. It restored most of the thyroid architecture and function, revealing a significant protective effect of this vitamin. This experimental study demonstrates that BL abusing disrupts the immune system by different mechanisms and addresses BL, for the first time, as an autoimmune clinical hypothyroidism inducer drug. Additionally, VC is helpful in the management of BL abuse.

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.

Boldenone Undecylenate-Mediated Hepatorenal Impairment by Oxidative Damage and Dysregulation of Heat Shock Protein 90 and Androgen Receptors Expressions: Vitamin C Preventive Role.

Boldenone Undecylenate (BLD) is a synthetic derivative of testosterone and a widely used anabolic androgenic steroid. The health risk of BLD use as a pharmaceutical or dietary supplement is still underestimated and under-reported. Vitamin C (VC) has been recognized as an antioxidant with prominent hepatorenal protective effects. This study investigated the possible preventive activity of VC against BLD-induced hepatorenal damage. Forty adult male Wistar rats were classified into five groups: control, vehicle control, VC (orally given 120 mg/kg b. wt./day), BLD (intramuscularly injected 5 mg/kg b. wt./week), and BLD + VC-treated groups. The experiment continued for eight weeks. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. Serum contents of total protein (TP), albumin (ALB), globulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and very-low-density lipoprotein-cholesterol (VLDL-C) were also assayed. Urea, creatinine, and uric acid levels were determined together with sodium and potassium electrolytes measuring. Moreover, oxidative stress indicators including reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GSR) as well as malondialdehyde (MDA) levels were measured in both hepatic and renal tissues. Corresponding histological examination of renal and hepatic tissues was conducted. Besides, immunohistochemical evaluations for androgen receptors protein (AR) and heat shock protein 90 (Hsp 90) expressions were performed. BLD caused significant rises in serum ALT, AST, TP, ALB, TC, TG, LDL-C, VLDL-C, urea, creatinine, uric acid, potassium, and MDA levels. Further, BLD-injected rats showed significant declines in the serum levels of HDL-C, sodium, GSH, GPx, GST, and GSR. Besides, distinct histopathological perturbations were detected in renal and hepatic tissues of BLD-injected rats. AR and Hsp 90 immunoexpression were increased in hepatic and renal tissues. In contrast, VC significantly reversed the BLD-induced hepatorenal damage in co-treated rats but not ameliorated AR protein overexpression. VC could be an efficient preventive supplement for mitigating BLD-induced hepatorenal damage, possibly via controlling oxidative stress events.

Prevention of melamine-induced hepatorenal impairment by an ethanolic extract of Moringa oleifera: Changes in KIM-1, TIMP-1, oxidative stress, apoptosis, and inflammation-related genes.

BACKGROUND/AIMS: Melamine (ML) is a common food adulterant and contaminant. Moringa oleifera is a well-known medicinal plant with many beneficial biological properties. This study investigated the possible prophylactic and therapeutic activity of an ethanolic extract of M. oleifera (MEE) against ML-induced hepatorenal damage. METHOD: Fifty male Sprague Dawley rats were orally administered distilled water, MEE (800 mg/kg bw), ML (700 mg/kg bw), MEE/ML (prophylactically) or MEE+ML (therapeutically). Hepatic aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphate (ALP) in serum were measured. Serum total bilirubin, direct bilirubin, indirect bilirubin, protein, albumin, and globulin contents were also assayed, and urea and creatinine levels were determined. Moreover, antioxidant enzyme activity of glutathione peroxidase (GPx) and catalase (CAT) in serum levels were quantified. Complementary histological and histochemical evaluation of renal and hepatic tissues was conducted, and expression of oxidative stress (GPx and CAT) and apoptosis-related genes, p53 and Bcl-2, in hepatic tissue were assessed. In parallel, transcriptional expression of inflammation and renal injury-related genes, including kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), and tumor necrosis factor alpha (TNF-α) in the kidney tissue were determined. RESULTS: ML caused significant increases in serum levels of ALT, AST, ALP, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine. Further, ML treated rats showed significant reductions in serum levels of protein, albumin, globulin, GPx, and CAT. Distinct histopathological damage and disturbances in glycogen and DNA content in hepatic and renal tissues of ML treated rats were observed. KIM-1, TIMP-1, and TNF-α gene expression was significantly upregulated in kidney tissue. Also, GPx, CAT, and Bcl-2 genes were significantly downregulated, and p53 was significantly upregulated in liver tissue after ML treatment. MEE significantly counteracted the ML-induced hepatorenal damage primarily for co-exposed rats. CONCLUSION: MEE could be an effective therapeutic supplement for treatment of ML-induced hepato-renal damage, probably via modulating oxidative stress, apoptosis, and inflammation.

The Modulatory Role of Vitamin C in Boldenone Undecylenate Induced Testicular Oxidative Damage and Androgen Receptor Dysregulation in Adult Male Rats.

BACKGROUND: This study explored the effect of vitamin C (Vit-C) administration on the reproductive function of adult male Wistar rats injected with boldenone undecylenate (BOL). METHODS: Rats were randomly assigned into control, vehicle control, Vit-C (120 mg/kg b.wt./day, orally), BOL (received 5 mg/kg b.wt./week, IM) and BOL+Vit-C-treated groups. After eight weeks, hormonal assay, semen evaluation, testicular enzymes, and antioxidants biomarkers were assessed. Besides, the histopathological and immunohistochemical investigations of the androgen receptor (AR) expression were performed. RESULTS: The results revealed that serum testosterone, acid phosphatase, sorbitol dehydrogenase, sperm abnormalities, and testicular malondialdehyde were significantly incremented in the BOL-treated group. Testicular weight, sperm count, and sperm motility together with serum levels of luteinizing hormone, follicle-stimulating hormone, and estradiol, and testicular testosterone, catalase, superoxide dismutase, and reduced glutathione showed a significant decrease following BOL treatment. Besides, the AR immunoreactivity was significantly decreased in testicular tissues. Vit-C co-administration with BOL significantly relieved the BOL-induced sperm abnormalities, reduced sperm motility, testicular enzyme leakage, and oxidative damage. However, Vit-C could rescue neither BOL-induced hormonal disturbances nor AR down-regulation. CONCLUSIONS: The results provide further insight into the mechanisms of BOL-induced reproductive dysfunction and its partial recovery by Vit-C.

Neurotoxic, Hepatotoxic and Nephrotoxic Effects of Tramadol Administration in Rats.

The current study was performed to study the tramadol HCL toxic effects on the brain, liver, and kidney of adult male rats. Forty male adult albino rats were divided into 4 groups; the first one was considered as a control group, the others were orally administrated with 25, 50, and 100 b.wt. representing therapeutic, double therapeutic, and 4 times therapeutic doses, respectively, of tramadol HCL daily for 1 month. Serum and brain, hepatic, and renal tissues were collected for biochemical and molecular investigations. Tramadol HCL resulted in a significant increase in the brain serotonin, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malonyldialdehyde (MDA) levels with a significant decrease in the reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities. At the same line, hepatic and renal 8-OHdG and MDA levels showed a significant increase with a significant decrease in reduced glutathione (GSH), CAT, and SOD activities. In addition, hepatic and renal function parameters including serum alanine amino transferase (ALT), aspartate amino transferase (AST), urea, and creatinine were increased in a dose-dependent manner. At the molecular levels, hepatic cytochrome P5402E1 (CYP2E1), renal Kidney Injury Molecule-1 (KIM-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) showed also a significant increase in the expression levels. Histopathological evaluation of the brain confirmed the above biochemical results. In conclusion, tramadol HCL induced neurotoxic, hepatotoxic, and nephrotoxic effects in a manner relative to its concentration by affecting brain serotonin levels and hepatic and renal function, with the production of DNA damage and oxidative stress.

Argan oil ameliorates sodium fluoride-induced renal damage via inhibiting oxidative damage, inflammation, and intermediate filament protein expression in male rats.

Fluoride is widely distributed in the environment and has been associated with the development of different health hazards in animals and humans. Argan oil (AO) is a natural vegetable oil with various beneficial pharmacological effects. This study was designed to investigate the potential protective effect of AO supplementation as pre-treatment or co-treatment on sodium fluoride (NaF)-induced nephrotoxicity in rats. Male Sprague Dawley rats (n = 50) were randomly assigned to one of five equal groups: control group, AO-treated group (6 ml/kg b.wt.), NaF-treated group (20 mg/kg b.wt.), pre-treated group, and co-treated group. All rats were daily administered by oral gavage for duration of 30 days. The results showed that AO administration significantly improved renal function and antioxidant status and decreased the lipid peroxidation in NaF-treated rats. Additionally, AO normalized the renal levels of inflammatory markers and mRNA expression level of the intermediate filament protein genes, indicating NaF-induced podocyte damage was ameliorated. Histopathological evaluation of the kidney confirmed the before mentioned biochemical results. AO counteracted the nephrotoxic effects of NaF in rats particularly at co-exposure. These results concluded that AO administration exhibited a significant nephroprotective effect against renal injury induced by NaF in rats.

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.