Protective effects of N-acetyl-l-cysteine against penconazole-triggered hepatorenal toxicity in adult rats.

Introduction: Penconazole (PEN) is a widely applied triazole fungicide. This study sought to define the efficacy of N-acetyl-l-cysteine (NAC) in mitigating PEN-triggered hepatorenal toxicity in rats. Material and Methods: Twenty-eight adult male albino Wistar rats were assigned to four groups: a normal control (NC), a PEN group, a NAC group and a PEN+NAC group. Administration of PEN (50 mg/kg body weight (b.w.) every 2 days) and NAC (150 mg/kg b.w., daily) took place via oral gavage for 10 days. Results: Effective amelioration by NAC of PEN-induced liver and kidney dysfunction was indicated by a significant reduction in the circulating liver and kidney markers (aspartate aminotransferase, alanine aminotransferase, urea and creatinine). Attenuation of PEN-induced oxidative stress and lipid peroxidation in liver and kidney tissues was evident in a significant reduction in malondialdehyde and enhanced total antioxidant capacity. Moreover, NAC significantly reduced the histopathological alterations and the expression of tumour necrosis factor α in liver and kidney tissue. Furthermore, NAC maintained the messenger RNA levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1, and Kelch-like erythroid cell-derived protein 1 and prevented nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein upregulation caused by PEN. Conclusion: N-acetyl-1-cysteine protected against PEN-induced hepatorenal oxidative damage and inflammatory response via activation of Nrf2 and inhibition of NF-κB pathways.

The ameliorative effect of N-acetylcysteine against penconazole induced neurodegenerative and neuroinflammatory disorders in rats.

Penconazole (PEN) is a widely used systemic fungicide to treat various fungal diseases in plants but it leaves residues in crops and food products causing serious environmental and health problems. N-acetylcysteine (NAC) is a precursor of the antioxidant glutathione in the body and exerts prominent antioxidant and anti-inflammatory effects. The present study aimed to explore the mechanistic way of NAC to ameliorate the PEN neurotoxicity in male rats. Twenty-eight male rats were randomly divided into four groups (n = 7) and given the treated material via oral gavage for 10 days as the following: Group I (distilled water), Group II (50 mg/kg body weight [bwt] PEN), Group III (200 mg/kg bwt NAC), and Group IV (NAC + PEN). After 10 days all rats were subjected to behavioral assessment and then euthanized to collect brain tissues to perform oxidative stress, molecular studies, and pathological examination. Our results revealed that PEN exhibits neurobehavioral toxicity manifested by alteration in the forced swim test, elevated plus maze test, and Y-maze test. There were marked elevations in malondialdehyde levels with reduction in total antioxidant capacity levels, upregulation of messenger RNA levels of bax, caspase 3, and caspase 9 genes with downregulation of bcl2 genes. In addition, brain sections showed marked histopathological alteration in the cerebrum and cerebellum with strong bax and inducible nitric oxide synthetase protein expression. On the contrary, cotreatment of rats with NAC had the ability to improve all the abovementioned neurotoxic parameters. The present study can conclude that NAC has a neuroprotective effect against PEN-induced neurotoxicity via its antioxidant, anti-inflammatory, and antiapoptotic effect. We recommend using NAC as a preventive and therapeutic agent for a wide variety of neurodegenerative and neuroinflammatory disorders.

Atrazine-induced cell-mediated immunotoxicity in rabbits and the ameliorating role of glycyrrhizic acid.

The present study aimed to explain the mechanisms involved in cell-mediated immunotoxicity of atrazine (ATR) in rabbits and to evaluate the ameliorative role of glycyrrhizic acid (GA) against such toxic effects. Forty rabbits were assigned into 4 equal groups: control, ATR, GA, and ATR + GA groups. ATR (2475 ppm) and GA (60 µg of GA/ml of water) were administrated via food and drinking water, respectively, for 60 consecutive days. The cell-mediated immunotoxicity of ATR was clarified by the induced thymus immunotoxicity through downregulation of interleukin (IL)-9 gene and interferon-γ (IFN-γ) gene expression, upregulation in caspase-3, and significant decrease in the total leukocytic and lymphocyte counts. Histopathological investigations demonstrated severe depletion of lymphoid follicles in the medulla of the thymus gland. On the other hand, co-administration of GA for group 4 improved most of the undesirable impacts of ATR. In conclusion, the alteration in IL-9/IFN-γ expression may involve ATR-induced thymocyte apoptosis which may explain the mechanisms of ATR-induced cell-mediated immunotoxicity with a possible amelioration influence of GA administration.

Glycyrrhizic acid modulates the atrazine-induced apoptosis in rabbit spleen.

Atrazine (ATR) is a common herbicide used worldwide. It is a potent endocrine disruptor that causes hormonal imbalance. We investigated the modulatory role predisposed by glycyrrhizic acid (GA) against the hazardous effects caused by the ATR in the rabbit spleen. Sixty rabbits were assigned into 4 groups. The first group is the negative control; the ATR group received 1/10 of the oral LD 50 ATR; the GA group received 50 mg/kg body weight daily intraproteinally; and group 4 received both ATR and GA concurrently. ATR and GA administrations were done for 60 days. ATR-induced humoral immunotoxicity was illustrated by decreased serum total protein, albumin, and globulin levels and rabbit hemorrhagic disease virus antibody titer, 4 weeks after vaccination. Moreover, upregulation of spleen Fas and caspase-III genes was recorded in ATR-exposed rabbits. Clear splenocyte apoptosis was observed in the immunohistochemical examination by the caspase-III technique. GA diminished the ATR-induced splenocyte apoptosis through downregulation of Fas and caspase-III expressions. In conclusion, our findings bounced a new perspective into the mechanism by which ATR induces immunotoxicity and assumed the potential modulatory role of GA.

Molecular mechanisms of Cisplatin- induced placental toxicity and teratogenicity in rats and the ameliorating role of N-acetyl-cysteine.

The aim of the present study is to investigate the molecular mechanisms of Cisplatin- induced placental toxicity and teratogenicity in rats and the ameliorating role of N-acetyl-cysteine (NAC). Cisplatin was administrated intraperitoneally at 5 mg/kg.b.wt as a single dose on the 12th day of gestation while NAC was administered orally throughout gestation either alone or in concomitant injection of Cisplatin at 200 mg/kg.b.wt. Cisplatin + NAC group showed reduction in the elevated morphological, visceral and skeletal abnormalities as well as the morphological and histopathological changes in placenta compared to Cisplatin - treated rats. Importantly, NAC attenuated Cisplatin-induced placental apoptosis through down-regulation of Fas and Caspase-3 genes expression. In conclusion, induction of placental apoptosis by overexpression of Fas and Caspase-3 genes gives a new insight into the mechanism of Cisplatin teratogenicity. The protective role of NAC, on the other hand, was characterized by attenuation of Fas and Caspase-3 genes- mediated apoptosis.

The potential protective role of Akropower against Atrazine- induced humoral immunotoxicity in rabbits.

Introduction to the herbicide Atrazine (ATR) can bring about immunotoxicity, aside from other unfavorable results for the creature and human wellbeing. We went for clarifying the genotoxic mechanisms required in humoral immunotoxicity of Gesaprim® (ATR) and their constriction by Akropwer. Forty rabbits (1.5kg±20%) were utilized and appointed into 4 equal groups. group 1: control; group 2: Received Atrazine at 1/10 LD50 via food; group 3: Received Akropwer at 1ml/1l/day by means of drinking water; group 4: Received both Atrazine and Akropwer associatively by the same said dosage and course. Atrazine and Akropower exposure were accomplished for 60days. The genotoxic mechanisms of Atrazine- induced humoral immunotoxicity were explained by increased serum total protein and albumin levels, decreased RHDV antibody titer only after four weeks of vaccination and increased level of spleen Fas and Caspase-III genes expression in Atrazine-exposed rabbits. Marked splenocytes apoptosis were detected in the immunohistochemical examination by caspase-III technique and TUNEL assay. Akropower attenuated ATR-induced apoptosis through down-regulation of Fas and Caspase-III genes expression and suppression of their signaling pathway. In conclusion, induction of apoptosis by overexpression of Fas and Caspase-III genes gives a new insight into the mechanism of ATR immunotoxicity. The protective part of Akropower, on the other hand, was characterized by attenuation of Fas and Caspase-III genes mediated apoptosis.

Reproductive toxicity provoked by titanium dioxide nanoparticles and the ameliorative role of Tiron in adult male rats.

Titanium dioxide nanoparticles (TDN) are widely used in paints, plastics, ceramics, cosmetics, printing ink, rubber and paper. Tiron is a water soluble metal chelator and antioxidant. This study was designed to investigate the reproductive toxicity of TDN in male albino rats and the ameliorative role of Tiron to minimize such toxic effects. Eighty adult male albino rats were assigned into 4 equal groups, group 1: control; group 2: received TDN at 100 mg/kg/day orally for 8 weeks; group 3: received Tiron at 470 mg/kg/day intraperitoneally for 2 weeks (the last 2 weeks of the experimental period); group 4: received both TDN and Tiron by the same previously mentioned dose, route and duration. The results revealed that TDN provoked reproductive toxicity which was proved by the deteriorated spermogram picture, high incidence of micronucleated RBCs, elevated oxidative stress parameters and up regulation of Testin gene. Whereas, Tiron co-treatment ameliorated most of these toxic alterations. Our findings highlighted the protective role of tiron against TDN intoxication.

The mitigative effect of Raphanus sativus oil on chromium-induced geno- and hepatotoxicity in male rats.

To study the impact of radish oil on the possible genotoxic and hepatotoxic effects of hexavalent chromium, male rats were divided into 4 groups. Group 1 served as control, group 2 received radish oil at the recommended human therapeutic dose (0.07 mL/kg) by gavage, group 3 received sodium dichromate dihydrate (SDD) 520 mg/L in drinking water, and group 4 received both SDD and radish oil as previously mentioned in groups 2 and 3. All treatments were continued for six months. The results revealed that chromium exposure promoted oxidative stress with a consequently marked hepatic histopathological alterations, increased serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, alfa fetoprotein (AFP) levels, and micronucleated erythrocytes (MNE) % in peripheral blood. Moreover, COMET assay of hepatic DNA revealed that SDD exposure significantly decreased the intact cells %, head diameter, and head DNA % compared to control, indicating DNA damage. However, radish oil co-administration with SDD resulted in marked amendment in the altered parameters as detected by improved liver function markers (ALT and ALP) and AFP level, decreased lipid peroxidation, increased antioxidant markers, inhibited hepatic DNA damage and restored the hepatic histology by preventing the appearance of the altered hepatocytes' foci and decreasing chromium induced histopathological lesions. It could be concluded that radish oil was able to provide a convergent complete protection against the geno- and hepatotoxicity of chromium by its potent antioxidant effect.

Teratogenic effect of cisplatin in rats and the protective role of sodium selenate.

Eighty pregnant Sprague-Dawley rats were used in this study. They were allotted to four equal groups. The first group served as a control without any treatment while the other groups were given cisplatin, sodium selenate, and cisplatin+sodium selenate, respectively. Cisplatin was injected intraperitoneally in a dose of 5mg/kgb wt. on the 12th day of gestation while sodium selenate was administered orally in a dose of 0.5mg/kgb wt throughout gestation. Animals were sacrificed on the 20th day of gestation for fetal examination. Cisplatin produced significant elevation in the percentages of late resorption sites and dead foetuses compared with the control group. The mean foetal and placental weights were significantly reduced. Dwarf foetuses and subcutaneous (s/c) haemorrhage were also recorded in cisplatin-treated group. Visceral abnormalities were revealed in the form of dilated nares, anophthalmia and/or microphthalmia, dilated brain ventricles, hypertrophy of the heart, hypoplasia of the lung, hepatomegaly and dilated renal pelvis. Skeletal examination showed wide open fontanel, incomplete ossification of parietal and interparietal bones, incomplete ossification of sternum, reduction in the number or even complete absence of phalanges, sacral and/or caudal vertebrae. Histopathological examination of placentas in cisplatin-treated group revealed severe pathological alterations. Administration of sodium selenate significantly alleviated the afore-mentioned adverse effects of cisplatin on the fetuses and their placentas so we conclude that sodium selenate as an antioxidant has an effective protective role in cisplatin teratogenic effects.

The Remedial Efficacy of Spirulina platensis versus Chromium-Induced Nephrotoxicity in Male Sprague-Dawley Rats.

This study was conducted to investigate the possible protective effect of Spirulina platensis against chromium-induced nephrotoxicity. A total of 36 adult male Sprague-Dawley rats were divided into 4 equal groups (Gps). Gp1 served as control, rats of Gps 2, 3, and 4 were exposed to Spirulina platensis (300 mg/kg b.wt per os) and sodium dichromate dihydrate (SDD) via drinking water at concentration of 520 mg /l respectively. Chromium administration caused alterations in the renal function markers as evidenced by significant increase of blood urea and creatinine levels accompanied with significant increase in kidney's chromium residues and MDA level as well as decreased catalase activity and glutathion content in kidney tissue. Histologically, Cr provoked deleterious changes including: vascular congestion, wide spread tubular epithelium necrobiotic changes, atrophy of glomerular tuft and proliferative hyperplasia. The latter was accompanied with positive PCNA expression in kidney tissues as well as DNA ploidy interpretation of major cellular population of degenerated cells, appearance of tetraploid cells, high proliferation index and high DNA index. Morphometrical measurements revealed marked glomerular and tubular lumen alterations. On contrary, spirulina co-treatment with Cr significantly restored the histopathological changes, antioxidants and renal function markers and all the previously mentioned changes as well.

Studies on the potential protective effect of cinnamon against bisphenol A- and octylphenol-induced oxidative stress in male albino rats.

Among the numerous chemicals discharged into the surrounding environment, bisphenol A (BPA) and octylphenol (OP) have been shown to increase oxidative stress in body by disturbing the prooxidant/antioxidant balance of cells. Cinnamon aqueous extract (CAE) is a natural product rich in polyphenolic compounds that have antioxidant activity. This study was designed to investigate the protective efficacy of CAE against oxidative disorders induced by BPA and OP in male albino rats. Animals were divided into 6 groups (10 rats each) and treated orally, 3 times weekly for 50 days. Group 1: control vehicle (olive oil); group 2 (25 mg BPA/kg b.wt./day); group 3 (25 mg OP/kg b.wt./day); group 4 (200 mg CAE/kg b.wt./day); group 5 (CAE 2 h before BPA administration); and group 6 (CAE 2 h before OP administration). BPA- and OP-exposed groups showed insignificant elevation in the final body weight; weight gains and significant reduction only in the relative kidneys weight. Also, BPA and OP exposure resulted in significant increase in serum urea, creatinine and kidney, brain, testicular malondialdehyde (MDA) levels. Significant reduction in tissues reduced glutathione (GSH) contents; catalase (CAT) and superoxide dismutase (SOD) activities were also recorded in BPA and OP exposed animals compared to the control vehicle group. Pretreatment with CAE 2 h either before BPA or OP administration ameliorated the BPA- and OP-induced body weight; weight gains and relative organs weight changes and biochemical adverse effects. CAE pretreatment also protected against the recorded pathological changes in kidney, brain and testis. In conclusion, CAE could ameliorate the oxidative toxic effects of BPA and OP indicating its protective antioxidant effect.

Immunotoxicity Following Pre- and Post-natal Aluminum Exposure in Rats.

The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the 6th day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the 15th day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams (G2 & G3) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group (G1) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopatho-logical changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.

Reproductive Toxicity Evaluation of Pestban Insecticide Exposure in Male and Female Rats.

Sexually mature male and female rats were orally intubated with the organophosphorus insecticide, Pestban at a daily dosage of 7.45 or 3.72 mg/kg bwt, equivalent to 1/20 and 1/40 LD50, respectively. Male rats were exposed for 70 days, while the female rats were exposed for 14 days, premating, during mating and throughout the whole length of gestation and lactation periods till weaning. The results showed depressed acetylcholinesterase (AChE) activity in the brain of parents, fetuses and their placentae in a dose-dependent manner. The fertility was significantly reduced with increasing the dose in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre-and postimplantation losses were significantly increased. The incidence of resorptions was more pronounced in treated female compared to male group and was dose dependant. The behavioral responses as well as fetal survival and viability indices were altered in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group and occurred in a dose-related manner. The recorded morphological, visceral, and skeletal anomalies were significantly increased with increasing the dose in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to Pestban would cause adverse effects on fertility and reproduction.

Characterization of the Heavy Metals Contaminating the River Nile at El-Giza Governorate, Egypt and Their Relative Bioaccumulations in Tilapia nilotica.

This study was carried out to measure the concentration of heavy metals (Pb, Mn, Cr, Cd, Ni, Zn, and Cu) in water and Bolti fish (Tilapia nilotica) samples collected from Rasheed branch of River Nile, north of El-Giza Governorate, Egypt by atomic absorption spectrophotometry. The investigated districts through which the branch passes include El-Manashi, Gezzaya, El Katta, Abo Ghaleb and Wardan. Based on WHO and FAO safety reference standards, the results of the current study showed that water and fish tissues were found to contain heavy metals at significantly variable concentration levels among the investigated districts. They were polluted with respect to all the metals tested at Gezzaya district. However, the levels of analyzed metals in water and fish tissues were found lower than legal limits in other districts. The heavy metals showed differential bioaccumulation in fish tissues of the different districts as the accumulation pattern (as total heavy metal residues) was district dependant as follow: Gezzaya > Wardan > El Katta > Abo Ghaleb > El Manashi.

Effects of ammonium metavanadate on fertility and reproductive performance of adult male and female rats.

Vanadium is a ubiquitous trace metal present in most plant and animal tissues. Environmental exposure to trivalent and pentavalent inorganic vanadium compounds has been related to impaired different phases of reproduction. Therefore, the effects of a pentavalent inorganic vanadium compound on general reproductive performance and fertility were investigated in male and female rats. Sexually mature male and female rats were exposed to 200 ppm ammonium metavanadate in drinking water. Male rats were exposed for 70 days, while the female rats exposed for 14 days premating, during mating, and throughout the whole length of gestation and lactation periods till weaning. The effects on male sex organ weights and fertility were evaluated at the end of exposure period. However, the effects on female fertility as well as developmental and postnatal effects were evaluated throughout the exposure period. The fertility was significantly reduced in both treated groups, with more pronounced suppressive effects in the male treated group. The number of implantation sites and the number of viable fetuses were significantly reduced in pregnant females of both treated groups. However, the number of resorptions, dead fetuses, and pre- and postimplantation losses were significantly increased. The incidence of resorptions was significantly increased in treated female group compared with untreated female group. The behavioral responses as well as fetal survival and viability indices were decreased in both treated groups during the lactation period. The incidence of these effects was more pronounced in the treated female group. The morphological, visceral, and skeletal anomalies were recorded significantly increased in fetuses of both treated groups, with more pronounced effects on fetuses of treated females. In conclusion, the exposure of adult male and female rats to ammonium metavanadate would cause adverse effects on fertility and reproduction.