Rescue of cone and rod photoreceptor function in a CDHR1-model of age-related retinal degeneration.

Age-related macular degeneration (AMD) is the most common cause of untreatable blindness in the developed world. Recently, CDHR1 has been identified as the cause of a subset of AMD that has the appearance of the "dry" form, or geographic atrophy. Biallelic variants in CDHR1-a specialized protocadherin highly expressed in cone and rod photoreceptors-result in blindness from shortened photoreceptor outer segments and progressive photoreceptor cell death. Here we demonstrate long-term morphological, ultrastructural, functional, and behavioral rescue following CDHR1 gene therapy in a relevant murine model, sustained to 23-months after injection. This represents the first demonstration of rescue of a monogenic cadherinopathy in vivo. Moreover, the durability of CDHR1 gene therapy seems to be near complete-with morphological findings of the rescued retina not obviously different from wildtype throughout the lifespan of the mouse model. A follow-on clinical trial in patients with CDHR1-associated retinal degeneration is warranted. Hypomorphic CDHR1 variants may mimic advanced dry AMD. Accurate clinical classification is now critical, as their pathogenesis and treatment are distinct.

Postoperative pancreatic fistula after pancreaticogastrostomy versus pancreatojejunostomy after pancreatic resection, a comparative systematic review and meta-analysis.

BACKGROUND: In patients undergoing pancreaticoduodenectomy (PD), there has been some evidence favoring pancreaticogastrostomy (PG) over pancreatojejunostomy (PJ) in the occurrence of postoperative pancreatic fistulas (POPF) and considering PG as a safer anastomotic technique. However, other publications revealed comparable incidences of POPF attributed to both techniques. The current work attempts to reach a more consolidated conclusion about such an issue. METHODS: This is a systematic review and meta-analysis that analyzed the studies comparing PG and PJ during PD in terms of the rate of POPF occurrence. Studies were obtained by searching the Scopus, PubMed Central, and Cochrane Central Register of Controlled Trials databases. RESULTS: 35 articles published between 1995 and 2022 presented data from 14,666 patients; 4547 underwent PG and 10,119 underwent PJ. Statistically significant lower rates of POPF (p = 0.044) and clinically relevant CR-POPF (p = 0.043) were shown in the PG group. The post-pancreatectomy hemorrhage (PPH) was significantly higher in the PG group, while no significant difference was found between the two groups in the clinically significant PPH. No statistically significant differences were found regarding the amount of intraoperative blood loss, length of hospital stay, DGE, overall morbidity rates, reoperation rates, or mortality rates. The percentage of male sex in the PG group and the percentage of soft pancreas in the PJ group seem to influence the odds ratio of CR-POPF (p = 0.076 and 0.074, respectively). CONCLUSION: The present study emphasizes the superiority of PG over PJ regarding CR-POPF rates. Higher rates of postoperative hemorrhage were associated with PG. Yet, the clinically significant hemorrhage rate was comparable between the two groups.

Outcomes of revisional surgery options after inadequate sleeve gastrectomy: A comprehensive network meta-analysis.

BACKGROUND: Despite the success of sleeve gastrectomy (SG) in of weight loss and treatment of the medical problems associated with obesity, some concerns have arisen about the need for revisional surgeries after SG in some patients. This study aimed to present an updated and comprehensive comparison among the presently available revisional surgeries employed explicitly in cases of inadequate outcomes after SG, which is the most frequently performed bariatric surgery in contemporary practice. METHODS: This network meta-analysis included studies that compared the outcomes of different revisional bariatric procedures after an inadequate outcome of SG. RESULTS: Searching across the electronic databases yielded 31 eligible articles. Re-SG was associated with the highest rate of significant complications. Patients treated with single anastomosis duodenal-ileal bypass (SADI) had a significantly higher percentage of total weight loss (%TWL) than those treated with one anastomosis gastric bypass (OAGB) and Roux-en-Y gastric bypass (RYGB). The percentage of excess weight loss (%EWL) at the end of the follow-up period was significantly higher in patients in the SADI group compared to those in the RYGB group and the OAGB, and re-SG exhibited the least values compared to SADI, biliopancreatic diversion with duodenal switch (BPD/DS), and OAGB. Significantly lower rates of reflux worsening/de novo development were observed in the SADI group compared to the OAGB group and the re-SG group, which showed significantly higher rates than SADI and RYGB. CONCLUSION: Our comprehensive network meta-analysis highlights SADI as a promising revisional option post-SG, demonstrating superior weight loss outcomes, lower significant complication rates, and a favorable impact on reflux compared to other procedures. While acknowledging the limitations of our study, these findings support the potential efficacy of SADI in addressing the challenges of inadequate weight loss after sleeve gastrectomy.

CRISPR Manipulation of Age-Related Macular Degeneration Haplotypes in the Complement System: Potential Future Therapeutic Applications/Avenues.

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss among the elderly in the developed world. Whilst AMD is a multifactorial disease, the involvement of the complement system in its pathology is well documented, with single-nucleotide polymorphisms (SNPs) in different complement genes representing an increased risk factor. With several complement inhibitors explored in clinical trials showing limited success, patients with AMD are still without a reliable treatment option. This indicates that there is still a gap of knowledge in the functional implications and manipulation of the complement system in AMD, hindering the progress towards translational treatments. Since the discovery of the CRISPR/Cas system and its development into a powerful genome engineering tool, the field of molecular biology has been revolutionised. Genetic variants in the complement system have long been associated with an increased risk of AMD, and a variety of haplotypes have been identified to be predisposing/protective, with variation in complement genes believed to be the trigger for dysregulation of the cascade leading to inflammation. AMD-haplotypes (SNPs) alter specific aspects of the activation and regulation of the complement cascade, providing valuable insights into the pathogenic mechanisms of AMD with important diagnostic and therapeutic implications. The effect of targeting these AMD-related SNPs on the regulation of the complement cascade has been poorly explored, and the CRISPR/Cas system provides an ideal tool with which to explore this avenue. Current research concentrates on the association events of specific AMD-related SNPs in complement genes without looking into the effect of targeting these SNPs and therefore influencing the complement system in AMD pathogenesis. This review will explore the current understanding of manipulating the complement system in AMD pathogenesis utilising the genomic manipulation powers of the CRISPR/Cas systems. A number of AMD-related SNPs in different complement factor genes will be explored, with a particular emphasis on factor H (CFH), factor B (CFB), and complement C3 (C3).

The neuroprotective effects of Piracetam on cisplatin-induced cognitive decline.

AIM: This work explores the effect of Cisplatin-a chemotherapeutic agent known to cause deterioration in cognitive function in cancer patients, and spatial memory in mice. It also investigates the potential neuroprotective effects of Piracetam, which is a nootropic drug recognized for improving cognitive ability. MATERIALS AND METHODS: The study incorporates four groups of mice receiving varied medication regimens, with memory tested using the Novel Location Recognition (NLR) method. RESULTS: The findings from our study revealed that memory decline and a suppression of cellular proliferation were observed in adult male mice subjected to Cisplatin treatment; furthermore, a decline in antioxidant efficacy within the hippocampal dentate gyrus was evident. Moreover, analysis of treatment effects on the animals' weight revealed that the Cisplatin and Piracetam group exhibited the most significant weight loss during drug administration. Despite the significant weight loss, the simultaneous use of Cisplatin and Piracetam demonstrated a notable improvement in memory and an augmentation of hippocampal proliferation and antioxidant effect. LIMITATIONS: It is important to note that our study was hampered by budget limits, a lack of additional animals, and mice's low tolerance for protracted treatment. CONCLUSIONS: Should the outcomes of Piracetam observed in this investigation be applicable to patients, it might offer a relatively straightforward approach to mitigate the cognitive impacts endured by cancer survivors following exposure to chemotherapy. Future research will be needed to study Piracetam's effect on mice with brain cancer after Cisplatin treatment in order to extrapolate the results onto cancer patients.

Exploring the modulation of MLH1 and MSH2 gene expression in hesperetin-treated breast cancer cells (BT-474).

The major mortality factor for women globally is breast cancer, and current treatments have several adverse effects. Hesperetin (HSP) is a flavone that occurs naturally with anti-tumor capabilities and has been investigated as a potential treatment for cancer. This study aimed to investigate the cytotoxic and anti-malignant potential of HSP on breast cancer cells (BT-474) and normal cells (MCF-10a). The results indicated that HSP has dose-dependent cytotoxicity in BT-474 and MCF-10a cells. The elevated concentration of HSP lowered cell viability and proliferation. The half-maximal inhibitory concentration (IC50) of HSP in BT-474 cancer cells after a 48-h exposure was 279.2 µM/ml, while the IC50 in normal cells was 855.4 µM/ml. The cytotoxicity of HSP was more significant in cancer cell lines than in normal cell lines and this aspect presents a favorable factor in utilizing the drug for the treatment of breast cancer. The apoptotic effect of HSP in BT-474 cells was investigated, and it was found that the higher the concentration of HSP more the cells underwent apoptosis. Furthermore, the highest concentration of HSP led to overexpression of the MLH1 and MSH2 genes in both breast cancer and normal cell lines. Overall, our study suggests that HSP has an anticancer effect on breast cancer cell lines, and the effect is concentration dependent.

Efficacy and Safety of Infliximab Versus Adalimumab in Adult Subjects With Moderate to Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis.

Ulcerative colitis (UC) is an inflammatory disorder affecting the colon, and typically, during the disease course, the condition may exacerbate, relapse, and remit. One of the most successful lines for inducing and maintaining clinical remission in subjects with UC is biological therapy with anti-tumor necrosis factor α (anti-TNF) agents, including adalimumab (ADA) and infliximab (IFX). This meta-analysis is an attempt to obtain complementary information driven by real-world experience (RWE) concerning the efficacy and safety of two of the most popular anti-TNFs in treating UC. This is a systematic review and meta-analysis of RWE studies comparing ADA and IFX as naïve anti-TNF agents for the treatment of subjects with UC. Studies were obtained by searching Scopus, Google Scholar, the Cochrane Central Register of Controlled Trials, Embase, and the PubMed Central databases. Patients treated with IFX showed significantly higher induction responses. No statistically significant difference was found in the comparison of response in the maintenance treatment period. Higher overall adverse events were related to IFX treatment, with serious adverse events that were nonsignificantly higher in the ADA-treated group. In conclusion, IFX demonstrated significantly higher induction responses compared to ADA in patients with moderate-to-severe UC. IFX was associated with higher overall adverse events, whereas serious adverse events were non-significantly higher in the ADA-treated group. IFX may be favored as a first-line agent for its induction efficacy, and the choice between IFX and ADA should be individualized based on comprehensive clinical evaluation.

Fluvoxamine Ameliorates the Damage to the Neuro-Behavioral Status of Rats Caused by the Administration of Valproic Acid by Preventing Cognitive Memory Deficits and Decreased Hippocampal Cellular Proliferation.

Fluvoxamine is a major antidepressant of the selective serotonin-reuptake inhibitor class, previously studied as a drug that improves cognitive memory by enhancing hippocampal cell division and proliferation. Valproic acid (VPA) is a commonly used antiepileptic drug and mood stabilizer that has negative effects on cognitive memory as it inhibits cellular division and proliferation in the hippocampus. This study assessed the protective effects of fluvoxamine treatment versus the memory impairment, decreased hippocampal cellular proliferation, and weight loss produced by VPA treatment. The cognitive memory of 40 male Sprague-Dawley rats was assessed by the novel object location (NOL) test. Immunostaining by Ki67 and glutathione peroxidase 1 (GPX-1) was performed to quantify the number of dividing cells in the subgranular zone (SGZ) of the dentate gyrus and to assess the antioxidant activity of different treatments, respectively. Results showed that the VPA group had fewer Ki67-positive cells than the control group (p < 0.001), indicating reduced hippocampal proliferation. In contrast, the VPA and fluvoxamine combination group showed increased proliferation (p < 0.001) compared to VPA alone. Notably, fluvoxamine treatment significantly differed in cell counts compared to other groups (p < 0.001). Fluvoxamine also attenuated the weight loss caused by VPA (p < 0.0001). Our data suggested that fluvoxamine therapy attenuated the VPA-induced decrease in SGZ cellular proliferation, memory, and weight in rats.

The Counter Effect of Exercise on Cisplatin-Induced Cognitive and Proliferation Impairments.

Background Cisplatin, a widely used chemotherapeutic agent, offers therapeutic benefits for cancer treatment but often leads to adverse effects on neurogenesis and oxidative stress, causing cognitive impairment. Concurrent physical activity has been proposed as a potential strategy to counteract these side effects. This study aimed to investigate the impact of physical exercise on cisplatin-induced cognitive impairment in a mouse model. Methods Adult male mice (n=45) were divided into three groups: control, cisplatin-treated (2.3 mg/kg), and exercise/cisplatin. Cisplatin was administered intraperitoneally over one month, while the exercise/cisplatin group underwent moderate-intensity exercise alongside cisplatin treatment. Spatial memory was evaluated using the novel object recognition (NOR) task, and hippocampal proliferation and oxidative stress were examined using Ki-67 and glutathione peroxidase (GPx) immunohistochemistry (IHC) staining, respectively. Statistical analyses were performed using the GraphPad Prism 4.0 software (GraphPad Software, San Diego, CA). Results The cisplatin-treated mice exhibited significantly lower preference index (PI) scores in the NOR task compared to the control (p<0.001) and exercise/cisplatin (p<0.001) groups. IHC staining revealed impaired hippocampal proliferation and increased oxidative stress in the cisplatin-treated group relative to the control and exercise/cisplatin groups. The introduction of a moderate-intensity exercise protocol appeared to mitigate the decline in hippocampal proliferation and oxidative damage induced by cisplatin. Additionally, cisplatin-treated mice experienced weight loss, while exercise attenuated this effect. Conclusion Cisplatin treatment resulted in decreased memory, hippocampal proliferation, and weight loss in mice. Concurrent moderate-intensity exercise seemed to alleviate these effects, suggesting a potential role for physical activity in ameliorating cisplatin-induced cognitive decline. This study underscores the importance of incorporating exercise as a complementary strategy to enhance cognitive outcomes in cancer patients undergoing cisplatin treatment.

Predisposing deleterious variants in the cancer-associated human kinases in the global populations.

Human kinases play essential and diverse roles in the cellular activities of maintaining homeostasis and growth. Genetic mutations in the genes encoding the kinases (or phosphotransferases) have been linked with various types of cancers. In this study, we cataloged mutations in 500 kinases genes in >65,000 individuals of global populations from the Human Genetic Diversity Project (HGDP) and ExAC databases, and assessed their potentially deleterious impact by using the in silico tools SIFT, Polyphen2, and CADD. The analysis highlighted 35 deleterious non-synonymous SNVs in the ExAC and 5 SNVs in the HGDP project. Notably, a higher number of deleterious mutations was observed in the Non-Finnish Europeans (26 SNVs), followed by the Africans (14 SNVs), East Asians (13 SNVs), and South Asians (12 SNVs). The gene set enrichment analysis highlighted NTRK1 and FGFR3 being most significantly enriched among the kinases. The gene expression analysis revealed over-expression of NTRK1 in liver cancer, whereas, FGFR3 was found over-expressed in lung, breast, and liver cancers compared to their expression in the respective normal tissues. Also, 13 potential drugs were identified that target the NTRK1 protein, whereas 6 potential drugs for the FGFR3 target were identified. Taken together, the study provides a framework for exploring the predisposing germline mutations in kinases to suggest the underlying pathogenic mechanisms in cancers. The potential drugs are also suggested for personalized cancer management.

Need for Staging Investigations in Newly Diagnosed Breast Cancer: Establishing Local Guidelines for Radiological Staging in Bahrain.

Objective: Staging workup and detection of distant metastases is important in newly diagnosed breast cancer in order to make treatment decisions and establish the prognosis. There is wide variation in current recommendations for staging investigations in breast cancer. Routine staging is performed for all patients in Bahrain because of lack of consistent guidelines. Optimization of the criteria for staging is important for identification of metastases, while minimizing harm and costs. The aim of this study was to evaluate factors associated with distant metastases in newly diagnosed patients with breast cancer, in order to establish local guidelines for proper selection of patients for systemic staging. Materials and Methods: Patients with newly diagnosed breast cancer at Salmaniya Medical Complex in Bahrain who underwent staging investigations between January 2016 and December 2022 were identified from a pathology database. Patients with previous history of cancer, synchronous tumors, bilateral breast cancer and ductal carcinoma in situ were excluded. Clinical, radiological and pathological data were retrospectively analyzed. Results: A total of 593 patients underwent staging computed tomography and bone scans or a PET scan. Distant metastases were identified in 20.7% of cases. M1 disease was significantly associated with multifocality/multicentricity, high grade tumors, hormone receptor-negative cancers, high Ki67 index, advanced tumor stage, node-positive disease, triple-negative breast cancer, use of PET scans and those who underwent neoadjuvant chemotherapy. Age was not associated with identification of distant metastases. Conclusion: The prevalence of distant metastases in this population of newly diagnosed patients with breast cancer was higher than previously reported. Routine staging of all patients at presentation was not indicated, especially for asymptomatic patients with early breast cancer. This study identified certain groups of patients with a higher risk of distant metastasis, in whom metastatic workup should be performed. These findings may allow for the development of a local guideline that addresses the question of which breast cancer patients need staging investigations for distant metastases.

Association of Hyperparathyroidism with Depression and Anxiety Among Chronic Hemodialysis Patients in the Al Baha Region, Kingdom of Saudi Arabia.

Introduction Anxiety and depression are prevalent psychological issues among hemodialysis patients, adversely affecting their well-being and treatment response. The study aims to identify the relationship between these mental health concerns and hyperparathyroidism in chronic hemodialysis patients from the Al Baha Region, Kingdom of Saudi Arabia. Methods This retrospective study included 143 chronic hemodialysis patients aged 18-85 years. Monthly laboratory records for parathyroid hormone (PTH) levels and the Hospital Anxiety and Depression Scale (HADS) for mental health assessment were utilized. Demographic information and the primary causes of end-stage renal disease were obtained through patient interviews. Statistical analyses, including chi-square tests, odds ratio, and significance tests, were performed to assess associations. Results Elevated PTH levels were associated with increased anxiety and depression in hemodialysis patients. Patients with PTH levels >400 pg/ml exhibited higher rates of abnormal HADS scores for anxiety and depression than those with PTH levels <400 pg/ml. Gender differences were evident, with women showing a higher predisposition to anxiety disorders and men having depression. Additionally, patients with PTH levels <150 pg/ml had a significantly higher proportion of the "normal" depression score than those with PTH levels >800 pg/ml. Conclusion The study underscores the association between hyperparathyroidism and adverse mental health outcomes in chronic hemodialysis patients. Maintaining optimal PTH levels plays a crucial role in mitigating anxiety and depression. Gender differences in mental health outcomes highlight the need for tailored interventions. Routine mental health assessments, utilizing tools such as the HADS, are important in the comprehensive care of hemodialysis patients.

Long-term clinical outcomes of intravascular imaging-guided percutaneous coronary intervention versus angiography-guided percutaneous coronary intervention in complex coronary lesions: a systematic review and meta-analysis.

Background: In this study, we aim to discuss the long-term clinical outcomes of intravascular ultrasound imaging-guided percutaneous intervention (IVUS-PCI) versus angiography-guided percutaneous coronary intervention (PCI) in complex coronary lesions over a mean period of 2 years. Methods: A systematic search and meta-analysis were conducted to assess the efficacy of using intravascular ultrasound or optical coherence tomography guidance in coronary artery stenting compared to angiography. Results: A total of 11 randomized controlled trials with 6740 patients were included. For the primary outcome, a pooled analysis (3.2 vs 5.6%). For secondary outcomes, the risk was significantly low in image-guided percutaneous intervention compared with angiography. Conclusion: Intravascular imaging-guided PCI is significantly more effective than angiography-guided PCI in reducing the risk of target lesion revascularization, target vessel revascularization, cardiac death, major adverse cardiovascular events and stent thrombosis.

A meta-analysis was conducted to compare intravascular ultrasound guidance/optical coherence tomography percutaneous coronary intervention with angiography percutaneous coronary intervention with target lesion revascularization as the primary outcome and target vessel revascularization, stent thrombosis, myocardial infarction, major adverse cardiovascular events, all cause death and cardiac death as the secondary outcomes.

Role of ascorbic acid versus silymarin in amelioration of hepatotoxicity induced by acrylamide in adult male albino rats: histological and immunohistochemical study / Rol del ácido ascórbico frente a la silimarina en la mejoría de la hepatotoxicidad inducida por acrilamida en ratas albinas macho adultas: estudio histológico e inmunohistoquímico

SUMMARY: Acrylamide (ACR) is a cytotoxic and carcinogenic material. It is a product of a Maillard reaction during the cooking of many types of fried fast food, e.g. potato chip fries, and chicken nuggets. ACR has a severe toxic effect on different body organs. This study investigates the hepatotoxic effect of ACR, and the protective effect of ascorbic acid and silymarin. For this purpose, forty adult, male, albino rats were divided into four groups and received the following treatments for fourteen days: Group I: (the control) normal saline; Group II: ACR only; Group III: ACR and ascorbic acid; and Group IV: ACR and silymarin. Under a light microscope, the liver from rats treated with ACR only presented disturbed liver architecture, degenerated hepatocytes, reduced glycogen contents, congested central vein, and increased collagen fibres with areas of fibrosis. Immunohistochemical examination revealed an increased mean number of CD68-, and α-SMA-positive cells. This indicates the presence of large numbers of stellate macrophages (Kupffer cells) and Hepatic stellate cells (HSCs). The combination of ACR with either ascorbic acid or silymarin resulted in less hepatic degeneration, less fibrosis and fewer CD68 and α-SMA positive cells compared to the ACR only group. In conclusion, treatment with silymarin or ascorbic acid along with ACR appears to alleviate ACR-induced hepatotoxicity with more protection in silymarin treated rats.

RESUMEN: La acrilamida (ACR) es un material citotóxico y cancerígeno. Es producto de la reacción de Maillard durante la cocción de muchos tipos de comida rápida y frita, por ejemplo: papas fritas y nuggets de pollo. ACR tiene un efecto tóxico severo en diferentes órganos del cuerpo. Este estudio investigó el efecto hepatotóxico del ACR y el efecto protector del ácido ascórbico y la silimarina. Con este fin, cuarenta ratas albinas machos adultas se dividieron en cuatro grupos y recibieron los siguientes tratamientos durante catorce días: Grupo I (control), solución salina normal; Grupo II, solo ACR; Grupo III, ACR y ácido ascórbico; y Grupo IV, ACR y silimarina. Bajo microscopio óptico, el hígado de ratas tratadas con ACR solo presentó alteración de su arquitectura, entre ellos hepatocitos degenerados, contenido reducido de glucógeno, vena central congestionada y aumento de fibras de colágeno con áreas de fibrosis. El examen inmunohistoquímico reveló un aumento del número medio de células CD68 y α-SMA positivas. Esto indica la presencia de un gran número de macrófagos estrellados (células de Kupffer) y células estrelladas hepáticas (HSC). La combinación de ACR con ácido ascórbico o silimarina resultó en menos degeneración hepática, menos fibrosis y menos células positivas para CD68 y α-SMA en comparación con el grupo de ACR solo. En conclusión, el tratamiento con silimarina o ácido ascórbico junto con ACR parece aliviar la hepatotoxicidad inducida por ACR.

Atomoxetine enhances memory and proliferation in adult male rat hippocampus

Atomoxetine (ATX) is a noradrenaline reuptake inhibitor used to treat Attention deficit hyperactive syndrome (ADHD), or improve cognition in normal subjects. The cognitive effects of ATX require inputs from the hippocampus. Moreover, proliferation is said to be located in the dentate gyrus (DG) of the hippocampus.In the present study, we hypothesised that ATX improves memory and proliferation of the adult rat hippocampus. To test this hypothesis, 5 intraperitoneal injections of ATX (30 mg/kg/day) over 5 consecutive days were delivered to rats. 30 minutes after the last injection, spatial memory was tested using the Novel location recognition (NLR) test. Proliferation of hippocampal cells was quantified using immunohistochemistry for the proliferative marker Ki67. ATX-treated rats showed cognitive enhancement in the NLR task and increase in cell proliferation in the Subgranular zone (SGZ) of the DG, compared to saline-treated controls. The results demonstrate that ATX is able to enhance cognition through increasing the levels of proliferation in the adult rat brains

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Ginger and vitamin C as protective agents against oxidative stress and liver injury induced by methyl parathion

Methyl parathion is one of the highly toxic organophosphorus (OP) compounds. It induces hepatotoxicity, which might be related to generation of reactive oxygen species. This study was carried out to investigate the protective roles of vitamins C and ginger against hepatotoxicity induced by methyl parathion in male albino rats.Sixty male albino rats were randomly divided into 6 groups (ten rats each). Group I was considered as controls. Animals of groups II, III and IV were given methyl parathion (2 mg/kg), ginger (200 mg/kg) and vitamin C (100 mg/kg) respectively. Groups V and VI were given ginger (200 mg/kg) and vitamin C (100 mg/kg) respectively 2 hours before methyl parathion administration. All animals were treated orally, once daily, for four weeks. Blood and liver samples were obtained for biochemical, immunohistochemistry and histopathological examinations.Administration of either ginger or vitamin C along with methyl parathion significantly reduced the alanine aminotransferase (ALT) and malondialdehyde (MDA) levels in rats compared to those only treated with methyl parathion. Treatment with either ginger or vitamin C in combination with methyl parathion resulted in increased level of reduced glutathione compared to the methyl parathion treated group. However, oral ginger significantly increased glutathione-S-transferase levels compared to the control group, and this may outbalance the protective value of ginger over vitamin C to guard against liver injury and oxidative stress. The immunohistochemical and histopathological examinations showed that ginger or vitamin C combination with methyl parathion resulted in less hepatocytes degeneration and milder portal tract infiltration compared to the methyl parathion group.In conclusion, pre-treatment with either ginger or vitamin C appears to alleviate methyl parathion-inducted hepatotoxicity. However, their protective role is still limited and needs further investigation

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