Mitigating effect of gallic acid on zinc oxide nanoparticles and arsenic trioxide-induced spermatogenesis suppression, testicular injury, hormonal imbalance, and immunohistochemical changes in rats.

The current study compared the effects of incorporated exposure to arsenic trioxide (As) and zinc oxide nanoparticles (ZnONPs) on male reproductive hormones, oxidative stress, and inflammatory biomarkers in adult rats to each metal alone. A defensive trial with gallic acid (GA) has also been studied. A total of 60 adult male Sprague Dawley rats were categorized into six groups: control, GA (20 mg/kg), ZnONPs (100 mg/kg), As (8 mg/kg), ZnONPs with As, and GA concurrently with ZnONPs and As at the same previous doses. The regimens were applied for 60 days in sequence. Current findings showed significant weight loss in all study groups, with testicular weights significantly decreased in the As and combined groups. Testosterone, follicular stimulating hormone, and luteinizing hormone serum levels were also considerably reduced, while serum levels of estradiol increased. Inducible nitric oxide synthase (iNOS) immunoexpression was significantly upregulated while proliferating cell nuclear antigen (PCNA) was downregulated. Moreover, there was a significant elevation of testicular malondialdehyde, reduction of testicular superoxide dismutase, and glutathione peroxidase with disruptive testes, prostate glands, and seminal vesicle alterations in all experimental groups with marked changes in the combined group. Additionally, the present results revealed the protective effects of GA on ZnONPs and As adverse alterations in rats. GA enhanced sperm picture, oxidant status, and hormonal profile. Also, it modulates iNOS and PCNA immunoexpression and recovers the histoarchitecture of the testes, prostate glands, and seminal vesicles. Ultimately, GA may be a promising safeguarding agent against ZnONPs and As-induced disturbances to reproductive parameters.

Influence of titanium dioxide nanoparticles and/or cadmium chloride oral exposure on testicular morphology, oxidative stress, and apoptosis in rats: Ameliorative role of co-enzyme Q10.

Background and objectives: Little is known about the implications of titanium dioxide nanoparticles (TiO2NPs) and cadmium chloride (Cd) co-exposure on the male reproductive system in mammals. As a result, this study researched the effects of oral TiO2NPs and/or Cd exposure on male reproduction and testicular functions. Additionally, a mitigation trial with co-enzyme Q10 (CoQ10) has also been conducted. Methods: In a 60-day experiment, seven experimental groups, each containing 10 male Sprague Dawley rats, were orally given distilled water (control), corn oil (vehicle control), CoQ10 (10 mg/kg b.wt), TiO2NPs (50 mg/kg b.wt), Cd (5 mg/kg b.wt), TiO2NPs + Cd, and TiO2NPs + Cd + CoQ10. Then, sperm quality, male sex hormones, oxidative stress indications, Ti and Cd testicular residues, testes and accessory gland architecture, and apoptotic and inflammatory markers in rat testes were assessed. Results: TiO2NPs and/or Cd exposure negatively impacted body weight, weight gain, testicular weights, semen quality, serum reproductive hormones, oxidative stress parameters, and Caspase-3 and tumor necrosis factor (TNF-α) immunoreactions. Histopathological changes were recorded in testicular, seminal vesicle, and prostatic tissues. Yet, co-administration of CoQ10 with TiO2NPs and Cd substantially mitigated these adverse consequences. The most notable aspect is that it effectively lowered testicular tissue Ti and Cd levels. It also improved oxidant status, hormonal profile, and sperm picture. CoQ10 minimized the testicular damage implied by histological examination. Furthermore, CoQ10 significantly diminished TiO2NPs and Cd-induced Caspase-3 and TNF-α immunoexpression in testicular tissue. Conclusion: As a result, CoQ10 could be utilized as a safe remedy to protect male reproductive physiology from TiO2NPs and Cd damage.

Interactive effects of cadmium and titanium dioxide nanoparticles on hepatic tissue in rats: Ameliorative role of coenzyme 10 via modulation of the NF-κB and TNFα pathway.

This study investigated the effect of oral dosing of titanium dioxide nanoparticles (TNPs) and cadmium (Cd2+) on rat liver and the potential protective role of coenzyme Q10 (CQ10) against TNPs and Cd2+-induced hepatic injury. Seventy male Sprague Dawley rats were divided into seven groups and orally given distilled water, corn oil, CQ10 (10 mg/kg b.wt), TNPs (50 mg/kg b.wt), Cd2+ (5 mg/kg b.wt), TNPs + Cd2+, or TNPs + Cd2++CQ10 by gastric gavage for 60 successive days. The results showed that individual or mutual exposure to TNPs and Cd2+ significantly increased the serum levels of various hepatic enzymes and lipids, depleted the hepatic content of antioxidant enzymes, and increased malondialdehyde. Moreover, the hepatic titanium and Cd2+ content were increased considerably in TNPs and/or Cd2+-exposed rats. Furthermore, marked histopathological perturbations with increased immunoexpression of tumor necrosis factor-alpha and nuclear factor kappa B were evident in TNPs and/or Cd2+-exposed rats. However, CQ10 significantly counteracted the damaging effect of combined exposure of TNPs and Cd2+ on the liver. The study concluded that TNPs and Cd2+ exposure harm hepatic function and its architecture, particularly at their mutual exposure, but CQ10 could be a candidate protective agent against TNPs and Cd2+ hepatotoxic impacts.

Restorative effects of gallic acid against sub-chronic hepatic toxicity of co-exposure to zinc oxide nanoparticles and arsenic trioxide in male rats.

Background and objectives: This study aimed to assess the effect of zinc oxide nanoparticles (ZNPs) and/or arsenic trioxide (ATO) exposure on the liver of adult male Sprague Dawley rats. Moreover, the probable ameliorative impact of gallic acid (GA) against ZNPs and ATO-induced hepatotoxicity and the possible underlying mechanisms were evaluated. Methods: Sixty male Sprague Dawley rats were distributed into six groups. The 1st and 2nd groups were orally given distilled water (1 ml/kg) and 20 mg GA/kg b. wt, respectively. The 3rd and 4th groups were orally given 100 mg ZNPs/kg b. wt and 8 mg ATO/kg b. wt, respectively. The 5th group was co-administered ZNPs and ATO at the doses mentioned above. The last one was co-administered ZNPs, ATO, and GA at the earlier described doses. All tested compounds were orally given once a day for 60 successive days. Then, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic content of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) was evaluated. Moreover, Bcl-2 and Bax's reactive proteins were immunohistochemically detected, and Zn and As residual patterns in hepatic tissues were assessed. Results: ZNPs, ATO, and ZNPs+ATO-exposed rats showed significantly (P < 0.001) elevated serum AST (219%, 233%, and 333%), ALT (300%, 400%, and 475%), ALP (169%, 205%, and 294%), and total bilirubin (42%, 68%, and 109%) compared to the control ones. On the other hand, a significantly (P < 0.001) declined SOD (58%, 49%, and 43%) and GPx (70%, 63%, and 56%) but increased MDA (133%, 150%, and 224%) was recorded in the hepatic tissues of ZNPs, ATO, and ZNPs+ATO exposed rats, respectively, relative to the control rats. Moreover, the hepatic tissues of the ZNPs, ATO, and ZNPs+ATO exposed rats showed a significant (P < 0.001) decrease in Bcl-2 (28%, 33%, and 23%) but elevation in Bax (217%, 267%, and 236%) immunoreactivities compared to the control rats. These findings were consistent with the microscopic alterations in the hepatic architecture and accumulation of Zn and As. Furthermore, a notable hyperlipidemic condition was recorded following ZNPs and/or ATO exposure. On the contrary, GA notably reduced hepatic enzymes compared to ZNPs+ATO-exposed rats. Additionally, GA markedly improved ZNPs+ATO-afforded liver tissue damage and apoptotic events. Conclusion: Overall, GA oral dosing significantly mitigated the negative effects of ZNPs and ATO on the liver by improving the antioxidant defense system and controlling apoptotic changes.

Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats.

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production.

Ameliorative effects of quercetin against hepatic toxicity of oral sub-chronic co-exposure to aluminum oxide nanoparticles and lead-acetate in male rats.

The present study was designed to evaluate the probable ameliorative role of quercetin (QCN) against oxidative hepatotoxicity induced by aluminum oxide nanoparticles (Al2O3NPs) with a diameter < 30 nm and lead acetate (Pb) co-exposure in adult male Sprague-Dawley rats. Rats were weighed and allocated to seven groups (n = 10 each) and were treated orally via orogastric gavage for 60 successive days: rats of the 1st group were kept as control given distilled water (1 ml/kg), rats of the 2nd group received 2 ml/kg BW/day corn oil; rats of the 3rd group were administered 20 mg/kg BW QCN/day; rats of the 4th group received 100 mg/kg BW Al2O3NPs; rats of the 5th group received 50 mg/kg BW Pb; rats of the 6th group co-received Al2O3NPs and Pb at the same previous doses; and rats of the 7th group were co-administered Al2O3NPs, Pb, and QCN at the same previous doses. At the end of the experiment, serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total, direct, indirect bilirubin, triglycerides, total cholesterol, HDL, VLDL, and LDL were estimated. The hepatic oxidative stress biomarkers as superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx), were also evaluated. Finally, the histopathological and histomorphometric evaluations and the residues of Al and Pb in hepatic tissues were assessed. Al2O3NPs and/or Pb exposure significantly elevated lipid peroxidation levels and considerably altered the hepatic biochemical parameters; nevertheless, QCN significantly reduced hepatic enzymes compared to toxicant exposed groups. Additionally, QCN significantly improved Al2O3NPs-afforded liver tissue damage, as established in microscopic findings on the liver in the group treated with Al2O3NPs + Pb. Conclusively, QCN could be a candidate natural agent to safeguard the liver versus the co-harmful impacts of Al2O3NPs and Pb toxicity.

Involvement of tumor necrosis factor-α, interferon gamma-γ, and interleukins 1ß, 6, and 10 in immunosuppression due to long-term exposure to five common food preservatives in rats.

BACKGROUND/AIMS: Food preservatives are abundant in many products in the human environment. However, little is known about the impact of many food preservatives on the immune system and the immune related genes. Hence, this study aimed to evaluate the effects of five widespread food preservatives, including butylated hydroxyanisole (BHA), potassium sorbate (PS), sodium benzoate (SB), boric acid (BA), and calcium propionate (CP), on haemato-immune functions. METHOD: Sixty Sprague-Dawley rats were assigned to groups orally administered water (control), BHA (0.09 mg/kg), PS (4.5 mg/kg), SB (0.9 mg/kg), BA (0.16 mg/kg) or CP (0.18 mg/kg) for 90 consecutive days. Leukogram and erythrogram profiles were assessed. Nitric oxide and immunoglobulin levels together with phagocytic and lysozyme activities were estimated. Histologic examinations and histomorphometric analysis of splenic tissues were performed. Variations in the mRNA expression levels of tumour necrosis factor alpha (TNF-α), interferon gamma (IFNγ), interleukin (IL)-1ß, IL-6, and IL-10 were assessed. RESULTS: Anemic conditions, thrombocytopenia, leucocytopaenia simultaneous with lymphocytopaenia, monocytopenia, and esinopenia have been obvious following long term exposure to the tested food additives. Prominent exhaustion was noted in immunoglobulin and NO levels and in lysozyme and phagocytic activities. IFNγ, TNF-α, IL-1ß, IL-6, and IL-10 were obviously upregulated in the groups exposed to food preservatives. CONCLUSION: These results confirmed that continued exposure to high levels of BHA, PS, SB, BA, and CP has haematotoxic and immunotoxic effects. Furthermore, these adverse effects are mediated by cytokine production.

Impacts of Egyptian propolis extract on rat cerebellum intoxicated by aluminum silicate: histopathological studies.

Human is exposed to traces of aluminum silicate (AlS), i.e., cosmetics, pesticides. Accumulation of aluminum compounds including AlS is associated with neuropathological diseases, e.g., Alzheimer's disease. The aim of the current study is to investigate the neuroprotective effects of propolis extracts in AlS-induced cerebellum intoxication in rats. Forty adult rats were randomly divided into four groups (n = 10). The first group served as a control; the second group treated with 200 ml propolis/kg bwt. every other day by stomach gavage tube, third group was intraperitoneally injected with AIS (20 mg/kg) twice a week for 8 weeks, and the fourth group received propolis extract and AIS. At the end of 8 weeks, the cerebellum was harvested for further ultrastructure, histological, and histochemical investigations. Using electron microscopy, the ultrastructure of the cerebellar cortex of AlS intoxicated rats showed Purkinje cells with an irregular euchromatic nucleus and extremely increased invagination of the nuclear envelope. In addition, the cytoplasm revealed numerous damaged mitochondria (> 20%) as well as swollen lysosomes (> 40%) compared to controls. These AlS-related ultrastructure changes were to some extent normalized to < 10% and < 30% in case of mitochondria and lysosomes, respectively, if rats were co-treated with propolis extract. Further, histopathological examination showed that AlS-exposed rats revealed abnormal Purkinje cells with irregular size and shrank shape, evidence of pre-necrotic stage in the form of nuclear pyknosis, and condensed and frequent darkly stained cells in cerebellar layers. However, propolis extract co-administration reversed from 35 to 25% (p < 0.05) these alterations. The carbohydrate and protein contents were reduced in case of AlS treatment and surprisingly propolis co-treatment was able to rescue these neurotoxic effects. Propolis extract might have neuroprotective effects against AIS-induced toxicity. Further studies are required to identify the mechanism of the pharmacological action and optimal settings for medical testing of propolis extract.