Mechanistic insights into acetamiprid-induced genotoxicity on the myocardium and potential ameliorative role of resveratrol.

The current study aimed to explore the genotoxic impacts of the insecticide acetamiprid (ACP) on the myocardium and assess the ameliorative role of resveratrol (RSV). Male rats (10/group) were treated via oral route for 90 days: control; ACP (25 mg/kg); RSV (20 mg/kg); ACP+RSV. Peripheral blood micronucleus test, oxidative stress analysis, comet assay, 8-hydroxydeoxyguanosine and gene expression assessment were performed. The findings revealed that ACP has myocardial genotoxic effects, as demonstrated by increased micronucleus and 8-hydroxydeoxyguanosine formation and increased all comet parameters. Oxidative stress analysis demonstrated that ACP elevated H2O2 and NO levels while decreasing catalase and GST activities. Acetamiprid dysregulated the expression of genes related to oxidative stress and DNA damage response. However, RSV co-treatment resulted in significant protection against these genotoxic impacts. Resveratrol reduced DNA damage and restored the oxidative balance in the myocardium. Moreover, RSV modulated the Nrf2/HO-1 and Atm/P53 pathways, potentiating antioxidant defense and DNA repair.

Acetamiprid induces cardiotoxicity in rats by dysregulating α7 nAChR and its downstream targets: The ameliorative role of resveratrol.

Acetamiprid (ACP) is a novel neonicotinoid insecticide used for controlling insect pests. Resveratrol (RSV) is a natural polyphenol that possesses anti-oxidant, anti-inflammatory and anti-apoptotic actions. The current research explores the mechanism of ACP-induced cardiotoxicity and the alleviative effects of RSV. Male rats were allocated to four groups of ten each. Rats were treated daily for 90 days via oral route. Control rats received distilled water, ACP rats received 25 mg acetamiprid/kg, RSV rats received 20 mg resveratrol/kg and ACP + RSV rats received both ACP and RSV. ACP exposure increased serum creatine phosphokinase activity and cardiac troponin level. It also induced oxidative stress, as evidenced by the glutathione reduction, and malondialdehyde elevation, as well as the detrimental histopathological and immunohistochemical changes in the myocardium. Gene expression analysis revealed down-regulation in the mRNA expression of the survival-related genes α7 nAChR, Erk and Bcl-2, and up-regulation in the apoptosis-related genes Jnk, Bax and Caspase-3. Conversely, the concomitant administration of ACP with RSV alleviated most of the aforementioned toxic impacts. It can be concluded that ACP induces cardiotoxicity by dysregulating the mRNA expression of α7 nAChR and its downstream targets. Additionally, RSV is proved to be a promising ameliorative agent against ACP-induced cardiotoxicity.

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.

Audiological assessment of neonatal hyperbilirubinemia.

OBJECT: To evaluate the hearing of infants with history of neonatal hyperbilirubinemia using ABR. METHODS: A prospective randomized study carried on 100 infants whose hearing was assessed by ABR. Infants were allocated into two groups; case group which involve 60 infants with history of neonatal hyperbilirubinemia (bilirubin more than17 mg/dl and less than 30 mg/dl) and control group involve 40 healthy infants. Each group was divided into 3 groups based on their age i.e. ≤ 6 months, > 6-9 months &> 9-12 months. The evaluated variables were latency time & inter peak latency time. RESULTS: The mean latencies of wave III&V of ABR were significantly higher in the case group compared with the controls (P < 0.001) while the mean latencies of wave I did not show a significant difference between the two study groups (P > 0.05). The mean inter wave latencies I-III, I-V& III-V of ABR were significantly higher in the case group compared with the controls. There was a negative correlation between age and the studied variables. CONCLUSION: Hyperbilirubinemia have an adverse effect on neonatal hearing which was reflected by ABR parameters of this study.

Electrode impedance changes over time in MED El cochlear implant children recipients: Relation to stimulation levels and behavioral measures.

Objective: Electrode impedance measures resistance encountered by electric current passing through wires, electrodes and biological tissue. This study was designed mainly to evaluate changes in electrode impedance values and psycho-electric parameters changes (i.e. threshold levels, comfortable levels, and dynamic range) in cochlear implant patients over time. Methods: It was a prospective study encompassing 20 patients implanted by MED-EL device programd using behavioral programs. Electrical stimulation levels and electrode impedance values were examined at 0, 1, 3 and 6 months after the first fitting session. Results: Electrode impedance values were reduced from the time of activation to the 6 months visit. Most comfortable levels increased and dynamic range widened until the 6 months visit. There was an inverse correlation between impedance values and most comfortable level as well as dynamic range, over time. Conclusion: Frequent monitoring of electrode impedance (for device and electrodes problems) and electric stimulation levels (for better performance, mapping and habituation) during the first 6 months of implant use is recommended.

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.

Assessment of auditory functions in chronic hepatitis C patients treated by sofosbuvir.

OBJECTIVE: Evaluating the auditory function in patients with chronic hepatitis C treated with sofosbuvir and ribavirin. METHODS: This study involved 80 patients with chronic hepatitis C who agreed to receive sofosbuvir and ribavirin. All participants were subjected to baseline otological and audiological assessment just before treatment. The audiological assessment included standard pure tone audiometry, extended high-frequency audiometry, immitancemetry and otoacoustic emissions (OAEs) (transient and distortion product). According to baseline hearing threshold measurements, the study population was divided into 2 groups. Group 1 included 42 patients with normal hearing sensitivity (250-8000 Hz), and Group 2 included 38 patients with sensorineural hearing loss. After 24 weeks of therapy, otological and audiological assessments were repeated and compared between the two groups and before and after therapy. RESULTS: Post-treatment hearing threshold evaluation showed no significant difference from pretreatment evaluation at all tested frequencies. There was no statistically significant difference between pre and post-treatment otoacoustic emissions results. CONCLUSION: Therapy with sofosbuvir and ribavirin in chronic hepatitis C has no noticeable effects on cochlear functions.

Innovative perception on using Tiron to modulate the hepatotoxicity induced by titanium dioxide nanoparticles in male rats.

The extensive application of titanium dioxide nanoparticles (TiO2 NPs) in the food industry arouses a debate regarding the probable risk associated with their use. Several recent studies reported that most nanoparticles (NPs) have adverse actions on the liver. The objective of this study is to examine whether Tiron plays a modulatory role against apoptotic damage induced by TiO2 NPs in rat livers. Forty rats were randomly divided into 4 groups; a control group received phosphate-buffered saline, an intoxicated group received 100 mg/kg/day of TiO2 NPs for 60 days, a treated group received 470 mg/kg/day of Tiron for the last 14 days after TiO2 NPs administration, and a Tiron group received Tiron only as previously mentioned. Oral administration of TiO2 NPs significantly increased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). In the liver, TiO2 NPs increased oxidative stress through increasing lipid peroxidation and decreasing GSH concentration and the levels of the SOD and GPx enzymes. TiO2 NPs significantly upregulated the proapoptotic Bax gene and downregulated the antiapoptotic Bcl-2 gene. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Apoptotic lesions were also obvious in this group. Treatment with Tiron as an antioxidant significantly decreased serum biochemistry, ameliorated oxidative stress in hepatic tissue, upregulated Bcl-2, decreased Bax expression and attenuated the histopathology of hepatic injury. These findings indicate that Tiron effectively diminishes the hazardous effects of TiO2 NPs on rat liver.

Home particle repositioning maneuver to prevent the recurrence of posterior canal BPPV.

OBJECTIVE: To check the value of home particle repositioning maneuver in the prevention of the recurrence of posterior canal benign paroxysmal positional vertigo (pc-BPPV). METHODS: In this study, patients diagnosed as unilateral posterior canal BPPV were selected following an accurate evaluation using video goggle VNG system. All patients were managed by particle repositioning maneuver (PRM). Patients were instructed to do home PRM once weekly for five years. Then, they were divided into two groups (according to choice of patient to do PRM). The first group (control group) consisted of 144 patients who did not do home PRM; whereas the second group (study group) included 165 patients who performed home PRM. All patients (control & study groups) were followed up every four months for five years. RESULTS: The study found out that the recurrence rate of pc-BPPV in control group was 33 patients in the first year (27.2%), 11 patients in second year (9%), 5 patients in third year (4%), 3 patients in fourth year (2.5%) and 3 patients in fifth year (2.5%). The recurrence of pc-BPPV in the treated side (study group) of patients was reported as 5 patients in the first year (3.5%), 3 patients in the second year (2%), 2 patients in the third year (1.4%), 2 patients in the fourth year (1.4%), and 1 patient in the fifth year (0.7%). There was statistically significant difference between the control and the study groups regarding the recurrence rates in the first year follow up which was the highest in first four months. CONCLUSION: Home particle repositioning maneuver has the capacity to prevent the recurrence of pc-BPPV. It proved to be more successful and functional in minimizing the recurrence of the disease in the study than in the control group. Hence, home particle repositioning maneuver is highly recommended for one year at least in pc-BPPV.

Intratympanic Injections of Dexamethasone in Delayed Endolymphatic Hydrops: A Prospective Clinical Study.

OBJECTIVE: This study was designed to evaluate the effectiveness of intratympanic dexamethazone (ITD) for the treatment of ipsilateral delayed endolymphatic hydrops (DEH). METHODS: Forty-one patients were diagnosed with ipsilateral DEH. Only 37 patients completed this study. Patients were randomly divided into 2 groups. Group A (n = 16) received oral medication, and group B (n = 21) received ITD once weekly for 4 consecutive weeks. RESULTS: In group A, 6 patients showed improvement in their vertigo. Four patients (25%) showed complete vertigo control, and 2 patients (12.5%) showed substantial vertigo control. In group B, 21 patients showed improvement in their vertigo, 11 patients (52%) showed complete vertigo control, and 10 patients (47%) showed substantial vertigo control. Only 1 case did not show any improvement in their vertigo. CONCLUSION: ITD is proven to be a valuable and promising alternative modality for the management of ipsilateral DEH.

Corticosteroids versus vestibular rehabilitation in long-term outcomes in vestibular neuritis.

BACKGROUND: The management strategy for functional recovery after vestibular neuritis (VN) has not yet been established. Therapeutic choices involve corticosteroids, vestibular rehabilitation therapy (VRT) and the combination of corticosteroids with VRT. OBJECTIVE: The present study aimed to compare the efficacy of corticosteroids, vestibular rehabilitation, and combination of them in terms of subjective and objective improvement in patients with VN. METHODS: A prospective randomized study was conducted on 60 patients with acute vestibular neuritis within 3 days after symptom onset. The patients were divided into three groups; steroid group treated with corticosteroids (n = 20), VRT group (n = 20) managed with vestibular rehabilitation exercises and combination group (n = 20) received combined (corticosteroids and vestibular exercises). Groups were compared by caloric lateralization, vestibular myogenic potential amplitude asymmetry and Dizziness Handicap Inventory scores, both at presentation and up to 12 months. RESULTS: The study found no statistically significant difference between the three groups of the study at the end of the follow up period. CONCLUSION: Corticosteroids and VRT seem to be equivalently effective in patients with VN. The study proposes that corticosteroids may accelerate the recovery of VN, with no more beneficial role in the long-term prognosis of the disease.

Ocular vestibular evoked myogenic potential in patients with myasthenia gravis: A prospective clinical study.

OBJECTIVE: Myasthenia gravis (MG) is an archetypic disorder of neuromuscular junctions (NMJs) and autoantibody-mediated disease causing fatigable weakness of skeletal muscles with an ocular onset in up to 85%. The aim of this study was to detect extra ocular muscles (EOMs) abnormalities in MG patients using ocular vestibular evoked myogenic potential (oVEMP) n10 response. METHODS: The oVEMP was performed on 40 myasthenia gravis patients that were divided into three groups: newly diagnosed (10 patients), uncontrolled on treatment (15 patients) and controlled on treatment (15 patients) groups in addition to a control group of 10 subjects. Also a comparison of oVEMP response was held between patients with generalized and ocular MG. RESULTS: The oVEMP n10 showed significant difference between the 3 study groups and the control. The n10 showed no significant difference between the newly diagnosed group and the other 2 groups. There was also significant difference between uncontrolled and controlled on treatment group and between generalized and ocular types of myasthenic patients. CONCLUSION: The oVEMP can be usefully used in diagnosis of new MG patients as regard n10 amplitude, threshold and AR except n10 latency with no therapeutic or monitoring value of oVEMP in MG.

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.

Tiron ameliorates oxidative stress and inflammation in titanium dioxide nanoparticles induced nephrotoxicity of male rats.

Although the widespread use of titanium dioxide nanoparticles (TiO2 NPs), few studies were conducted on its hazard influence on human health. Tiron a synthetic vitamin E analog was proven to be a mitochondrial targeting antioxidant. The current investigation was performed to assess the efficacy of tiron against TiO2 NPs induced nephrotoxicity. Eighty adult male rats divided into four different groups were used: group I was the control, group II received TiO2 NPs (100mg\Kg BW), group III received TiO2 NPs plus tiron (470mg\kg BW), and group IV received tiron alone. Urea, creatinine and total protein concentrations were measured in serum to assess the renal function. Antioxidant status was estimated by determining the activities of glutathione peroxidase, superoxide dismutase, malondialdehyde (MDA) level and glutathione concentration in renal tissue. As well as Renal fibrosis was evaluated though measuring of transforming growth factor-ß1 (TGFß1) and matrix metalloproteinase 9 (MMP9) expression levels and histopathological examination. TiO2 NPs treated rats showed marked elevation of renal indices, depletion of renal antioxidant enzymes with marked increase in MDA concentration as well as significant up-regulation in fibrotic biomarkers TGFß1 and MMP9. Oral administration of tiron to TiO2 NPs treated rats significantly attenuate the renal dysfunction through decreasing of renal indices, increasing of antioxidant enzymes activities, down-regulate the expression of fibrotic genes and improving the histopathological picture for renal tissue. In conclusion, tiron was proved to attenuate the nephrotoxicity induced by TiO2 NPs through its radical scavenging and metal chelating potency.

Extending the concept of weighted CT dose index to elliptical phantoms of various aspect ratios.

The purpose of this study was to extend the concept of weighted CT dose index ([Formula: see text]) to the elliptical phantoms. Based on the published body dimension data, eight body aspect ratios were chosen between 1 (perfectly circular) and 1.72 (extremely elliptical). For each aspect ratio, two elliptical cylinders were created digitally to represent adult and pediatric bodies. Their cross-sectional areas were identical to the standard 32- and 16-cm CTDI phantoms. For each phantom, [Formula: see text] at center and periphery were simulated for tube voltages between 70 and 140 kVp using a validated Monte Carlo program. The simulations also provided the average dose over the cross-sectional area, [Formula: see text]. Values of [Formula: see text] and [Formula: see text] allowed linear systems of equations to be established, from which central and peripheral weighting coefficients were solved. Regardless of phantom shape, only two weighting coefficients were needed: [Formula: see text] for the central [Formula: see text] and [Formula: see text] for the average of the four peripheral [Formula: see text]'s. Over the full range of aspect ratios, [Formula: see text] increased linearly from 0.37 to 0.46, whereas [Formula: see text] decreased linearly from 0.63 to 0.54, allowing the concept of [Formula: see text] to be readily extended to the elliptical phantoms. When cross-sectional area (hence volume) was kept constant, all phantoms had the same [Formula: see text] regardless of shape.

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.