Avicenna Journal of Medical Biochemistry
Volume:12 Issue: 1, Winter and Spring 2024

 Snake venoms have been the subject of intense studies to understand the mechanisms involved in toxicity. Limited information is available regarding the Egyptian Spitting Cobra’s oxidative stress and hematological profile (Naja nubiae).

 The present study aimed to evaluate the oxidative stress produced by the venom of N. nubiae and determine its hematotoxic effects in rats.

 The adult male Albino rats (N=30) were subcutaneously (SC) injected with a physiological saline solution in the control group. The SC injection of snake venom in groups 2 and 3 was 1/4 and 1/2 of the LD50 (0.32 mg/kg and 0.65 mg/kg body weight, respectively). Blood samples were collected at 30, 120, and 360 minutes post-injection for biochemical and hematological assays in both control and treated groups. Levels of oxidative stress biomarkers, including lipid peroxidation (LPO), protein carbonyl content (PCC), and nitric oxide (NO) were estimated. Antioxidants agents comprising glutathione (GSH) level, activities of superoxide dismutase (SOD), and catalase (CAT) were also evaluated.

 The results showed that the effects of snake venom on blood cells are dose-dependent. Furthermore, significant alterations (P≤0.05) were observed in the hemoglobin (Hb) concentration, packed cell volume (PCV), and the number of red blood cells (RBCs) in response to a low dose of venom at the 30-minute time. In contrast to the control group, the venom induced a substantial elevation in LPO, NO, and PCC levels, indicating a disturbance in redox equilibrium. Additionally, significant reductions were detected in the GSH levels as well as SOD and CAT activities in all treated groups.

 Overall, the cytotoxicity’s potential to induce oxidative stress may reduce its antioxidant systems, leading to redox disturbance and hematological alteration.

 Hydrogen sulfide (H2 S) is the third most crucial gas that is produced inside the body, and at physiological levels, it increases a wide range of health properties, such as anti-inflammatory antioxidant effects.

 This study aimed at evaluating the impact of H2 S administration on oxidative stress (OS) in the heart and liver tissues of diabetic rats.

 Twenty-eight Wistar rats were randomly divided into 4 groups, namely, the healthy control group, the diabetic group, and diabetic groups treated with 50 µM/kg and 100 µM/kg of H2 S. After 60 days of treatment, the animals were sacrificed, and biochemical and OS markers were determined using colorimeter methods. In addition, the liver tissue underwent histological assessment.

 The findings revealed that H2 S controlled the weight of rats and significantly decreased fasting blood sugar (FBS) in the treatment group with a dose of 50 µM/kg and 100 µM/kg (P<0.05) compared to the diabetic animals. Further, insulin concentration and insulin resistance in the H2 S 100 µM/kg group decreased in comparison to the diabetic group (P<0.05). The levels of triglyceride, cholesterol, atherogenic index, and low-density lipoprotein in H2 S-treated animals were markedly lower than in the diabetic group (P<0.05). The results of OS parameters demonstrated that H2 S 100 µM/kg reduced the malondialdehyde in the heart tissue compared to the diabetic group (P<0.05). The histological assessment also confirmed the effectiveness of H2 S in improving liver morphology and parenchymal structure.

 According to the results of this study, H2 S can be considered a suitable therapeutic agent to prevent diabetes complications.

Background:

 Plant secondary metabolites have been reported to offer a wide variety of medicinal purposes, including protection against heavy metal toxicity.

Objectives: 

This study aimed to investigate the potentiality of naringenin a flavonoid in ameliorating the antioxidant defense system of neural and cardiac cells against aluminum chloride (AlCl3 ) toxicity in rats.

Methods: 

The rats were divided into control (group 1), AlCl3 -treated (2), AlCl3+Naringenin-treated (3), and Naringenin-treated (4) groups. During experimentation, group 2 received an oral dose of 100 mg/kg/BW of AlCl3 , and group 3 received 100 mg/kg/BW of AlCl3 and 50 mg/ kg/BW of naringenin. In addition, group 4 received 50 mg/kg/BW of naringenin each day, while group 1 and all groups received a normal diet and water ad libitum for 30 days. The animals were sacrificed, and then blood, brain, and heart tissues were collected for biochemical and histological studies.

Results: 

The results revealed that naringenin administration ameliorates the antioxidant defense system (catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx], and glutathione transferase) in AlCl3 toxicity in neural and cardiac tissues. AlCl3 caused oxidative tissue damage, showing a significant increase in malondialdehyde (MDA) (P<0.05) in both tissues. The levels of neurotransmitter acetylcholine esterase, nitric oxide, and lactate dehydrogenase (LDH) in the rats of group 3 were significantly (P<0.05) higher compared with AlCl3 -intoxicated rats. Furthermore, the AlCl3 -administered group had significantly (P<0.05) elevated levels of total cholesterol (TC), triglycerides, and low-density lipoprotein-cholesterol, with reduced high-density lipoprotein-cholesterol levels in comparison to the naringenin-treated and control groups. Naringenin treatment normalized the lipid profile. Histological analysis using the hematoxylin and eosin staining method revealed that AlCl3 caused degenerative changes in the cerebellum and cardiac tissues, which were ameliorated by co-treatment with naringenin.

Conclusion: 

Naringenin has the potential to mitigate AlCl3 -induced oxidative stress (OS) in the neural and cardiac tissues of rats by enhancing the antioxidant defense system and reversing tissue injuries in the brain and heart.

Exposure to methyl methane sulfonate (MMS), an alkylating agent, induces DNA damage, increasing cellular and metabolic sensitivity, leading to cellular demise and a delay in the cell cycle. This delay is attributed to changes in global transcription regulation, resulting in significant alterations in the proteome. Numerous studies have focused on transcriptome changes post-MMS treatment. However, cellular proteomic changes remain underexplored. This brief literature review is based on the assessment of studies obtained from several PubMed, Web of Science, and Scopus databases and Google Scholar using specific keywords. The article is based on manuscripts published between 2005 and 2024. Proteomic analysis identified 53 proteins, with 36 upregulated, 10 downregulated statuses, and a few exhibiting no or negligible changes. MMS exposure reflected changes in the phosphorylation status of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP-II) and a gross change in the transcriptome. Literature also supports the proteome change of the RNAP-II complex and ~1640 peptides, corresponding to 27 interacting proteins and the twelve RNAP-II subunits. The identified proteins were involved in DNA repair and energy pathway modulation. Notably, significant changes were observed in enzymes mostly related to carbohydrate and amino acid metabolism, predominantly, glycolysis, the fate of pyruvate, and the biosynthetic pathways of amino acid metabolism. The available literature supports a co-regulated response to MMS-induced DNA damage involving both DNA repair mechanisms and metabolic pathways.

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency and impaired glucose regulation. While daily insulin therapy is life-saving, many patients struggle to achieve optimal glycemic control, leading to microvascular complications affecting various organs, including the kidneys and the liver. This review aims to summarize the current state of knowledge regarding the pathogenesis of hepatic and renal complications in T1D, highlight recent advances in potential therapeutic targets, and provide evidence-based recommendations for mitigating end-organ damage. Chronic hyperglycemia drives diabetic complications through several interrelated mechanisms, including increased polyol pathway flux, advanced glycation end-product (AGE) formation, protein kinase C activation, and mitochondrial reactive oxygen species overproduction. In the liver, these processes contribute to non-alcoholic fatty liver disease, with up to 50% of T1D patients developing hepatic steatosis. Diabetic nephropathy, affecting 25%–40% of long-term T1D patients, is characterized by glomerular basement membrane thickening, mesangial expansion, and tubulointerstitial fibrosis. Recent innovations in T1D management include genomics and precision medicine approaches, gut microbiome modulation, nanomedicine, and artificial intelligence-driven glucose monitoring systems. Emerging immunotherapies aim to fundamentally modify the autoimmune response in T1D. Mitigating T1D complications requires intensive glycemic control, targeted pharmacotherapy, and lifestyle modifications. Emerging therapies and precision medicine approaches offer promising avenues. Ongoing research into molecular mechanisms remains crucial for developing novel interventions and improving long-term outcomes in T1D patients.

 Bacillus Calmette-Guérin (BCG) immunotherapy is a standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) after tumor resection. However, not all patients respond to BCG therapy. Reliable prognostic markers are needed to predict treatment outcomes.

 This study reviewed the prognostic value of systemic immune-inflammation index (SII) and related markers in BCG response.

 A systematic literature search was conducted in PubMed, Web of Science, and Scopus databases from inception to October 2023 for studies on SII index, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in bladder cancer patients receiving BCG therapy. Four retrospective studies involving 1124 patients met the inclusion criteria and were included in qualitative synthesis. Three studies were included in the meta-analysis of progression-free survival (PFS) and recurrence-free survival (RFS). Data on study characteristics and demographics, follow-up duration, cancer stage/grade, and pre-treatment marker levels were extracted. Hazard ratios (HRs) were pooled using a random effects model.

 Elevated pre-treatment SII was associated with significantly worse PFS (HR: 3.72, 95% CI: 1.74-7.98, P<0.001) and RFS (HR: 3.72, 95% CI: 1.42-9.77, P=0.007). However, significant heterogeneity was found among trials in the overall survival (OS) (I2 =83.49, P=0.002) and RFS (I2 =89.69%, P=0.002). In multivariate analysis, SII>672.75 was an independent predictor of BCG failure (OR: 2.229, 95% CI: 1.172-4.238, P=0.015). NLR, PLR, and MLR also showed potential prognostic value with area under the curve (AUC) values ranging from 0.592 to 0.663 for predicting non-response to BCG therapy. Specifically, NLR>3.0435, PLR>123.4398, and MLR>0.1995 were significantly associated with non-response to BCG (P<0.001 for all). In univariate analysis, BCG non-response was associated with high pre-treatment levels of PLR, NLR, and MLR (P<0.001).

 Pre-treatment SII and other inflammatory markers may predict poor outcomes after BCG immunotherapy in bladder cancer patients. SII holds promise as an accessible prognostic biomarker that can guide treatment decisions. Further large prospective studies are warranted to validate these preliminary findings.

A theory is much broader than a hypothesis or a conjecture if it can provide explanations for a wide range of observations while remaining robust to challenges through experimentation. There is a paucity of such theories in biology. The main motivation behind this research was to propose a broad theory of biological life and to explore whether it can be used as a framework for understanding health and disease conditions. A conceptual and theoretical approach was followed for this purpose. Extensive exploration and analysis of the biomedical literature in a non-systematic but purposeful manner were undertaken. They were then extrapolated using a top-down approach to identify the fundamental systems mediating life processes. Two attributes must exist for the survival of any biological life form, including the ability to grow and the ability to self-protect. These two functions are performed by the metabolic system and immune system, respectively. It is proposed that all other processes and every entity in a life form are involved in conducting these two fundamental functions. It is inferred that both of these functions exhibit the universal characteristics of duality and complementarity, features that cut across disciplines. A given life form may thus be biased toward one of the two processes mediated by the immune system and metabolic system at different stages in its life history. Identifying factors that confer bias might provide a better understanding of biology with direct implications for medicine. It is proposed that life and disease could be the result of the interplay of immune and metabolic systems acting complementarily. Other physiological systems lend support to the balancing act between the immune and metabolic systems in a biological life form.