The Protective Effects of Taurine, a Non-essential Amino Acid, Against Metals Toxicities: A Review Article.

Taurine is a non-proteinogenic amino acid derived from cysteine. It is involved in several phenomena such as the regulation of growth and differentiation, osmoregulation, neurohormonal modulation, and lipid metabolism. Taurine is important because of its high levels in several tissues such as the central nervous system (CNS), heart, skeletal muscles, retinal membranes, and platelets. In this report, we present the functional properties of taurine indicating that it has potential effects on various metal toxicities. Therefore, a comprehensive literature review was performed using the Scopus, PubMed, and Web of Science databases. According to the search keywords, 61 articles were included in the study. The results indicate that taurine protects tissues against metal toxicity through enhancement of enzymatic and non-enzymatic antioxidant capacity, modulation of oxidative stress, anti-inflammatory and anti-apoptotic effects, involvement in different molecular pathways, and interference with the activity of various enzymes. Taken together, taurine is a natural supplement that presents antitoxic effects against many types of compounds, especially metals, suggesting public consumption of this amino acid as a prophylactic agent against the incidence of metal toxicity.

Anti-inflammatory, antioxidant and anti-mitophagy effects of trans sodium crocetinate on experimental autoimmune encephalomyelitis in BALB/C57 mice.

Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund's adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1ß and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1ß and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.

Renoprotective effect of thymoquinone against rhabdomyolysis-induced acute kidney injury in the rat model.

Objectives: Rhabdomyolysis leads to the release of myoglobin, sarcoplasmic proteins, and electrolytes into the blood circulation causing acute kidney injury (AKI). Thymoquinone, a natural compound found in Nigella sativa seeds, has antioxidant and anti-inflammatory effects. This investigation assessed the renoprotective effect of thymoquinone on rhabdomyolysis-induced AKI in rats. Materials and Methods: Male Wistar rats were categorized into six groups (n = 6): 1. Control: (normal saline), 2. Glycerol (50 ml/kg, single dose, IM), 3-5: Glycerol + thymoquinone (1, 2.5 and 5 mg/kg, 4 days, IP), 6. Thymoquinone (5 mg/kg). On day 5, serum and kidney tissue were isolated and the amounts of serum creatinine and blood urea nitrogen (BUN), renal malondialdehyde (MDA), glutathione (GSH.), tumor necrosis factor-alpha (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL), and pathological changes were evaluated. Results: Glycerol increased creatinine, BUN, MDA, TNF-α, and NGAL levels. It decreased GSH amounts and caused renal tubular necrosis, glomerular atrophy, and myoglobin cast in kidney tissue. Co-administration of glycerol and thymoquinone reduced creatinine, BUN, histopathological alterations, and MDA levels, and enhanced GSH amounts. Administration of glycerol and thymoquinone (5 mg/kg) had no significant effect on TNF-α amount but decreased NGAL protein levels. The administration of thymoquinone (5 mg/kg) alone did not display a significant difference from the control group. Conclusion: Rhabdomyolysis from glycerol injection in rats can cause kidney damage. Thymoquinone may attenuate renal dysfunction and oxidative stress. However, the TNF-α level was not significantly affected. Further studies are needed to explore the potential therapeutic effects of thymoquinone in managing AKI.

Trans-sodium crocetinate suppresses apoptotic and oxidative response following myoglobin-induced cytotoxicity in HEK-293 cells.

Objectives: Rhabdomyolysis (RM) is a serious fatal syndrome. The RM leads to acute kidney injury (AKI) as a fatal complication. The belief is that RM-induced AKI is triggered by myoglobin (MB). MB activates oxidative and apoptotic pathways. Trans-sodium crocetinate (TSC) is obtained from saffron. It has anti-oxidant and renoprotective effects. This research was designed to assess the mechanisms of MB-induced cytotoxicity in HEK-293 cells (human embryonic kidney cells) as well as the possible effects of TSC against MB-induced cytotoxicity. Materials and Methods: HEK-293 cells were exposed to diverse concentrations of TSC (2.5, 5, 10, 20, 40, 80, and 100 µM) for 24 hr. Then, MB (9 mg/ml) was added to the cells. After 24 hr, cell viability was measured through MTT, and the values of ROS generation were calculated using DCFH-DA assay. Also, autophagy and apoptosis markers in cells were assessed by western blot analysis. Results: MB decreased viability and increased ROS levels in HEK-293 cells. However, pretreatment of HEK-293 cells with TSC for 24 hr reduced the cytotoxicity and ROS production caused by MB. Furthermore, MB enhanced both the apoptosis (cleaved caspase-3 and Bax/Bcl-2 ratio) and autophagy markers (LC3II/I ratio and Beclin-1) in HEK-293 cells. On the other hand, TSC pretreatment condensed the levels of autophagy and apoptosis criteria in response to MB cytotoxicity. Conclusion: TSC has a positive effect in preventing MB-induced cytotoxicity in HEK-293 cells by increasing anti-oxidant activity and regulation of apoptotic and autophagy signaling pathways.

An exosomal approach for oral delivery of resveratrol: Implications for inflammatory bowel disease treatment in rat model.

AIMS: Resveratrol (RSV) is a polyphenolic substance found in numerous natural products. Despite the wide range of therapeutic activities, including antioxidant and anti-inflammatory effects, the poor pharmacokinetic characteristics decrease the RSV bioavailability following oral administration. Milk-derived exosomes (MEXOs), as a class of natural nanocarriers, are promising candidates for oral drug delivery approaches. MAIN METHODS: The current study developed RSV-loaded MEXOs to enhance the RSV oral bioavailability, introducing a suitable exosomal formulation for suppressing colon inflammation in acetic acid-induced rat models. KEY FINDINGS: The results showed a remarkable encapsulation efficiency of 83.33 %. The in vitro release profile demonstrated a good retaining capability in acidic conditions (pH 1.2) and a considerable release in a simulated duodenal environment (pH 6.8). According to the permeability study, encapsulation of RSV improved its transportation across the Caco-2 monolayer. Moreover, the in vivo and histological analysis results proved that the RSV-MEXOs formulation successfully alleviates the inflammation in colitis rat models and effectively relieves the colitis. SIGNIFICANCE: Our findings suggest that MEXOs should be of great attention as promising oral drug delivery vehicles for further clinical evaluations.

Can daily consumption of enriched fatty acids diet be effective in improving metabolic syndrome? An attractive paradox for walnut kernel.

Imagine consuming a daily diet rich in fatty acids to help treat diseases such as hypertension and obesity. This concept presents an attractive paradox. In particular, consuming walnut kernels is beneficial for treating diseases associated with metabolic syndrome (MetS), including type 2 diabetes, cardiovascular disease, dyslipidemia, and obesity. Different parts of the Juglans regia tree (family Juglandaceae), including its leaves, green husks, bark, and septum, have shown promising effects on pathological conditions related to MetS. The therapeutic advantages of consuming walnut kernels for MetS can be attributed to the presence of polyunsaturated fatty acids and polyphenolic compounds such as juglone and ellagic acid. Diets enriched with walnut kernel have a positive impact on MetS complications by reducing diastolic blood pressure, improving blood lipid profiles, lowering fasting blood sugar levels, and increasing insulin sensitivity. The potential cellular mechanisms responsible for these benefits involve activating the cholesterol hemostasis pathway by inhibiting sterol regulatory element-binding proteins (SREBPs), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cholesteryl ester transfer protein (CETP). Furthermore, other by-products of walnuts, such as leaves and green husks, have also demonstrated effectiveness in managing MetS. These findings highlight the potential of incorporating walnut-based products into our diets as a natural approach to combating MetS and its complications.

Therapeutic potential of hypnotic herbal medicines: A comprehensive review.

Insomnia affects millions of people worldwide, prompting considerable interest in herbal remedies for its treatment. This review aims to assess the therapeutic potential of such remedies for insomnia by analyzing current scientific evidence. The analysis identified several herbs, including Rosmarinus officinalis, Crocus sativus, Rosa damascena, Curcuma longa, Valeriana officinalis, Lactuca sativa, Portulaca oleracea, Citrus aurantium, Lippia citriodora, and Melissa officinalis, which show promise in improving overall sleep time, reducing sleep latency, and enhancing sleep quality. These plants act on the central nervous system, particularly the serotonergic and gamma-aminobutyric acid (GABA)ergic systems, promoting sedation and relaxation. However, further research is necessary to fully understand their mechanisms of action, optimal dosages, and treatment protocols. Combining herbal medicines with conventional treatments may offer an effective natural alternative for those seeking medication. Nevertheless, individuals should consult their healthcare provider before using herbal remedies for insomnia. While this review provides evidence supporting their use, additional high-quality studies are needed to firmly establish their clinical efficacy.

Attenuation of acrylamide-induced neurotoxicity by supplementation of sitagliptin in Wistar rats.

Objectives: Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-2 diabetes medication with neuroprotective properties. The effects of sitagliptin against neurotoxicity stimulated by ACR were examined. Materials and Methods: Male Wistar rats were classified as follows: 1. Control (normal saline, 11 days, IP), 2. ACR (50 mg/kg, 11 days, IP), 3. ACR (11 days, days 11-20 normal saline), 4-7. ACR+sitagliptin (5, 10, 20, and 40 mg/kg, 11 days, IP), 8. ACR+sitagliptin (10 mg/kg, days 6-11), 9. ACR+sitagliptin (10 mg/kg, days 6-20), 10. Sitagliptin (40 mg/kg, 11 days), 11. ACR+vitamin E (200 mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue. Also, IL-1ß, TNF-α, and caspase-3 levels were assessed in the cortex by western blotting. Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-1ß, and caspase-3 cleaved levels. Supplementation of sitagliptin (10 mg/kg) along with ACR, in 3 protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (10 mg/kg) from days 6 to11 reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (10 mg/kg) with ACR dropped the amounts of TNF-α and caspase-3 cleaved proteins in cortex tissue but did not affect the IL-1ß level. Conclusion: Sitagliptin disclosed preventive and therapeutic effects on ACR neurotoxicity. Sitagliptin possesses antioxidant, anti-inflammatory, and anti-apoptotic properties and inhibits CR neurotoxicity in rats.

The molecular mechanisms of ginkgo (Ginkgo biloba) activity in signaling pathways: A comprehensive review.

BACKGROUND: One of the most unique plants that have ever grown on the planet is Ginkgo biloba L., a member of the Ginkgoaceae family with no close living relatives. The existence of several differently structured components of G. biloba has increased the chemical variety of herbal therapy. Numerous studies that investigated the biochemical characteristics of G. biloba suggest this plant as a potential treatment for many illnesses. PURPOSE: Review the molecular mechanisms involved in the signaling pathways of G. biloba activity in varied circumstances and its potential as a novel treatment for various illnesses. METHODS: Studies focusing on the molecular processes and signaling pathways of compounds and extracts of G. biloba were found and summarized using the proper keywords and operators from Google Scholar, PubMed, Web of Science, and Scopus without time restrictions. RESULTS: G. biloba exerts its effects through its anti-inflammatory, anti-apoptotic, anti-cancer, neuroprotective, cardioprotective, hepatoprotective, antiviral, antibacterial, pulmoprotective, renoprotective, anti-osteoporosis, anti-melanogenic, retinoprotective, otoprotective, adipogenic, and anti-adipogenic properties. The most important mechanisms involved in these actions are altering the elevation of ROS formation, inhibiting NADPH oxidases activation, altering the expression of antioxidant enzymes, downregulating MAPKs (p38 MAPK and ERK, and JNK) and AP-1, increasing cAMP, inactivating Stat5, activating the AMPK signaling pathway, affecting Stat3/JAK2, NF-κB, Nrf-2, mTOR, HGF/c-Met, Wnt/ß-catenin and BMP signaling pathways, and changing the mitochondrial transmembrane potential, the Bax/Bcl-2 ratio, the release of Cyc from mitochondria to cytosol, the protein cleavage of caspases 3, 7, 8, 9, and 12, poly (ADP-ribose) polymerase, and MMPs levels. CONCLUSIONS: G. biloba and its components have gained attention in recent years for their therapeutic benefits, such as their anti-inflammatory, antioxidant, anti-apoptotic, and apoptotic effects. By understanding their molecular mechanisms and signaling pathways, potential novel medicines might be developed in response to the rising public desire for new therapies.

Carnosic acid mitigates doxorubicin-induced cardiac toxicity: Evidence from animal and cell model investigations.

Objectives: Utilization of doxorubicin (DOX) as a chemotherapy medication is limited due to its cardiotoxic effects. Carnosic acid exerts antioxidant, anti-inflammatory, besides cytoprotective effects. The objective of this study was to investigate the ability of carnosic acid to protect rat hearts and the MCF7 cell line against cardiotoxicity induced by DOX. Materials and Methods: The study involved the classification of male Wistar rats into seven groups: 1) Control 2) DOX (2 mg/kg, every 48h, IP, 12d), 3-5) Carnosic acid (10, 20, 40 mg/kg/day, IP, 16d)+ DOX, 6) Vitamin E (200 mg/kg, every 48h, IP, 16d)+ DOX 7) Carnosic acid (40 mg/kg/day, IP, 16d). Finally, cardiac histopathological alterations, ECG factors, carotid blood pressure, left ventricular function, heart-to-body weight ratio, oxidative (MDA, GSH), inflammatory (IL-1ß, TNF-α), plus apoptosis (caspase 3, 8, 9, Bcl-2, Bax) markers were evaluated. DOX toxicity and carnosic acid ameliorative effect were evaluated on MCF7 cells using the MTT assay. Results: DOX augmented the QRS duration, QA, RRI, STI, and heart-to-body weight ratio, and reduced HR, LVDP, Min dP/dt, Max dP/dt, blood pressure, boosted MDA, TNF-α, IL1-ß, caspase 3,8,9, Bax/Bcl-2 ratio, decreased GSH content, caused fibrosis, necrosis, and cytoplasmic vacuolization in cardiac tissue but carnosic acid administration reduced the toxic effects of DOX. The cytotoxic effects of DOX were not affected by carnosic acid at concentrations of 5 and 10 µM. Conclusion: Carnosic acid as an anti-inflammatory and antioxidant substance is effective in reducing DOX-induced damage by enhancing antioxidant defense and modifying inflammatory signal pathway activity and can be used as an adjunct in treating DOX cardiotoxicity.

The ameliorative effect of turmeric (Curcuma longa Linn) extract and its major constituent, curcumin, and its analogs on ethanol toxicity.

Ethanol toxicity is a major public health problem that can cause damage to various organs in the body by several mechanisms inducing oxidative stress, inflammation, and apoptosis. Recently, there has been a growing interest in the potential of herbal medicines as therapeutic agents for the prevention and treatment of various disorders. Turmeric (Curcuma longa) extracts and its main components including curcumin have antioxidant, anti-inflammatory, and anti-apoptotic properties. This review aims to evaluate the literature on the ameliorative effects of turmeric extracts and their main components on ethanol toxicity. The relevant studies were identified through searches of Google Scholar, PubMed, and Scopus without any time limitation. The underlying mechanisms of turmeric and curcumin were also discussed. The findings suggest that turmeric and curcumin ameliorate ethanol-induced organ damage by suppressing oxidative stress, inflammation, apoptosis, MAPK activation, TGF-ß/Smad signaling pathway, hyperlipidemia, regulating hepatic enzymes, expression of SREBP-1c and PPAR-α. However, the limited clinical evidence suggests that further research is needed to determine the efficacy and safety of turmeric and curcumin in human subjects. In conclusion, the available evidence supports the potential use of turmeric and curcumin as alternative treatments for ethanol toxicity, but further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Hepatoprotective effect of amifostine and WR-1065 on acetaminophen-induced liver toxicity on Wistar rats.

PURPOSE: The most important problem with acetaminophen is its hepatotoxicity. N-acetylcysteine (NAC) is used to treat the hepatotoxicity of acetaminophen. Due to the structural similarities of this compound with amifostine, we decided to test the effect of this substance and its metabolite, WR-1065, on the hepatotoxicity of acetaminophen. METHODS: The single-dose method contained 1. Control; 2. Acetaminophen (1 g/kg, gavage); 3-5. Acetaminophen + amifostine (100, 200, 400 mg/kg, i.p.); 6-8. Acetaminophen + WR-1065 (50, 100, 200 mg/kg, i.p.); and 9. Acetaminophen + NAC (100, 200 mg/kg, i.p.). The multiple-dose method included the same groups: amifostine (50, 100, 200 mg/kg), WR-1065 (25, 50, 100 mg/kg), and NAC (100 mg/kg). Then, animals were sacrificed, and blood samples were collected for measuring ALT, AST, ALP, and T-Bil, liver tissue for histopathological examination, MDA, and GSH amounts. RESULTS: Acetaminophen increased the levels of MDA, T-Bil, ALT, AST, and ALP, decreased GSH levels, and augmented necrosis, neutrophils, lymphocytes, and macrophages in the port space in single-dose and multiple-dose studies. Amifostine and WR-1065 significantly reduced the levels of MDA, T-Bil, ALT, AST, ALP, increased GSH content, and ameliorated histopathological alterations in a single-dose and multiple-dose method compared to the acetaminophen group. Moreover, NAC caused a significant decrease in the levels of MDA, T-Bil, ALT, AST, and ALP, and reduced GSH amounts in single-dose and multiple-dose studies. CONCLUSION: Amifostine and WR-1065 as antioxidant and hepatoprotective compounds are effective in reducing acetaminophen-induced hepatotoxicity with a similar effect to NAC and can be administered as an adjunct in the treatment of acetaminophen overdose.

Alpha-mangostin decreases high glucose-induced damage on human umbilical vein endothelial cells by increasing autophagic protein expression.

Objectives: Diabetes is a chronic disorder that occurs as a result of impaired glucose metabolism. In hyperglycaemic states, the balance between oxidative stress and antioxidant enzymes is disrupted leading to oxidative damage and cell death. In addition, impaired autophagy leads to the storage of dysfunctional proteins and cellular organelles in the cell. Hence, the cytoprotective function of autophagy may be disrupted by high glucose conditions. Alpha-mangostin (A-MG) is an essential xanthone purified from the mangosteen fruit. The different pharmacological benefits of alpha-mangostin, including antioxidant, anti-obesity, and antidiabetic, were demonstrated. Materials and Methods: We evaluated the protective influence of A-MG on autophagic response impaired by high concentrations of glucose in human umbilical vein endothelial cells (HUVECs). The HUVECs were treated with various glucose concentrations (5-60 mM) and A-MG (1.25-10 µM) for three days. Then, HUVECs were treated with 60 mM of glucose+2.5 µM of A-MG to measure viability, ROS, and NO content. Finally, the levels of autophagic proteins including LC3, SIRT1, and beclin 1 were evaluated by western blot. Results: The results expressed that high glucose condition (60 mM) decreased viability and increased ROS and NO content in HUVECs. In addition, LC3, SIRT1, and beclin 1 protein levels declined when HUVECs were exposed to the high concentration of glucose. A-MG reversed these detrimental effects and elevated autophagic protein levels. Conclusion: Our data represent that A-MG protects HUVECs against high glucose conditions by decreasing ROS and NO generation as well as increasing the expression of autophagy proteins.

Renoprotective effects of crocin against colistin-induced nephrotoxicity in a rat model.

Objectives: Colistin is used to treat multidrug-resistant gram-negative bacterial infections. It increases the membrane permeability of kidney cells, leading to kidney toxicity. Crocin, a carotenoid found in saffron, has anti-oxidant and nephroprotective properties. The present study aimed to explore the potential renoprotective effects of crocin against colistin-induced nephrotoxicity. Materials and Methods: Six groups of male Wistar rats were utilized: 1- Control (0.5 ml of normal saline, 10 days, IP); 2- Crocin (40 mg/kg, 10 days, IP); 3-Colistin (23 mg/kg, 7 days, IP); 4-6 Colistin (23 mg/kg, 7 days, IP)+ crocin (10, 20, 40 mg/kg, 10 days, IP). On day 11, rats were sacrificed and their blood and kidney samples were collected to measure creatinine, blood urea nitrogen (BUN), glutathione (GSH) levels, malondialdehyde (MDA), and histopathological alterations. Results: Colistin caused a significant increase in BUN, creatinine, and MDA, and a decrease in GSH compared to the control group. It also led to congested blood vessels, glomerular shrinkage, and medullary tubular degeneration. Co-administration of crocin with colistin resulted in a significant decrease in BUN and creatinine, increased GSH levels, and ameliorated the histopathological alterations compared to the colistin group. No significant difference was found between the control group and the crocin (40 mg/kg) group. Conclusion: It might be suggested that colistin can induce kidney damage by inducing oxidative stress. However, crocin shows protective effects against colistin-induced renal injury by acting as an anti-oxidant. Hence, crocin can be used as a supplement to reduce tissue and biochemical damage caused by colistin injection.

Effects of telmisartan on metabolic syndrome components: a comprehensive review.

Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It belongs to the drug class of angiotensin II receptor blockers (ARBs). Among drugs of this class, telmisartan shows particular pharmacologic properties, including a longer half-life than any other angiotensin II receptor blockers that bring higher and persistent antihypertensive activity. In hypertensive patients, telmisartan has superior efficacy than other antihypertensive drugs (losartan, valsartan, ramipril, atenolol, and perindopril) in controlling blood pressure, especially towards the end of the dosing interval. Telmisartan has a partial PPARγ-agonistic effect whilst does not have the safety concerns of full agonists of PPARγ receptors (thiazolidinediones). Moreover, telmisartan has an agonist activity on PPARα and PPARδ receptors and modulates the adipokine levels. Thus, telmisartan could be considered as a suitable alternative option, with multi-benefit for all components of metabolic syndrome including hypertension, diabetes mellitus, obesity, and hyperlipidemia. This review will highlight the role of telmisartan in metabolic syndrome and the main mechanisms of action of telmisartan are discussed and summarized. Many studies have demonstrated the useful properties of telmisartan in the prevention and improving of metabolic syndrome and this well-tolerated drug can be greatly proposed in the treatment of different components of metabolic syndrome. However, larger and long-duration studies are needed to confirm these findings in long-term observational studies and prospective trials and to determine the optimum dose of telmisartan in metabolic syndrome.

Can nonsteroidal anti-inflammatory drugs (NSAIDs) be repurposed for fungal infection?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of anti-inflammatory drugs widely used for the treatment of musculoskeletal disorders, mild-to-moderate pain, and fever. This review aimed to explain the functional role and possible mechanisms of the antifungal effects of NSAIDs alone or in combination with antifungal drugs in vitro and in vivo. Several studies reported that NSAIDs such as aspirin, ibuprofen, diclofenac, indomethacin, ketorolac, celecoxib, flurbiprofen, and nimesulide had antifungal activities in vitro, either fungistatic or fungicidal, against different strains of Candida, Aspergillus, Cryptococcus, Microsporum, and Trichophyton species. These drugs inhibited biofilm adhesion and development, and yeast-to-hypha conversion which may be related to a prostaglandin E2 (PGE2)/PGEx-dependent mechanism. Modulating PGE2 levels by NSAIDs during fungal infection can be introduced as a possible mechanism to overcome. In addition, some important mechanisms of the antifungal activities of NSAIDs and their new derivatives on fungi and host immune responses are summarized. Overall, we believe that using NSAIDs along with classical antifungal drugs has the potential to be investigated as a novel therapeutic strategy in clinical studies. Furthermore, combination therapy can help manage resistant strains, increase the efficacy of antifungal drugs, and reduce toxicity.

Preventive and therapeutic effects of azithromycin on acrylamide-induced neurotoxicity in rats.

BACKGROUND: Acrylamide (ACR) can induce neurotoxicity through different pathways, including oxidative stress and apoptosis. Azithromycin is well-known for its antioxidant and anti-apoptotic properties. OBJECTIVE: To evaluate the potential neuroprotective effect of azithromycin in an in vivo model of ACR-induced neurotoxicity, by investigating its impact on oxidative stress and apoptosis pathways. METHODS: Male rats were divided into eleven groups at random (n = 6). 1:control (vehicle), 2:ACR (50 mg/kg, 11 days, I.P.), 3-7:ACR+ azithromycin (3.1, 6.25, 12.5, 25, 50 mg/kg, 11 days, I.P.), 8-9:ACR+ azithromycin (3.1, 6.25 mg/kg, from day 3-11), 10: ACR+ vitamin E (200 mg/kg, every other day, I.P.), 11. Azithromycin (50 mg/kg). Following the treatment period, a gait score examination was performed, and malondialdehyde (MDA), glutathione (GSH), Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio and caspase-3 levels in the cerebral cortex were measured. RESULTS: Gait abnormality, a drop in GSH, and an increase in lipid peroxidation, Bax/Bcl-2 ratio, and caspase-3 levels were all significantly triggered by ACR in the cerebral cortex versus the control group. Azithromycin 3.1 and 6.25 mg/kg with ACR and azithromycin 6.25 mg/kg with ACR from day 3-11 ameliorated movement disorders caused by ACR. Azithromycin in all doses and both protocols along with ACR decreased the MDA level. Azithromycin (3.1, 6.25 mg/kg) along with ACR in both protocols increased the level of GSH, reduced the Bax/Bcl-2 ratio and caspase-3 amounts in the brain tissue versus the ACR group. CONCLUSIONS: Administration of azithromycin had both preventive and therapeutic effects on ACR-induced neurotoxicity through its antioxidant and antiapoptotic properties.

The protective effects of curcumin against cigarette smoke-induced toxicity: A comprehensive review.

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.

The effect of ellagic acid on the metabolic syndrome: A review article.

Objective: (s): Metabolic syndrome is a collection of metabolic abnormalities that includes hyperglycemia, dyslipidemia, hypertension, and obesity. Ellagic acid is found in various fruits and vegetables. It has been reported to have several pharmacological properties, such as antibacterial, antifungal, antiviral, anti-inflammatory, hepatoprotective, cardioprotective, chemopreventive, neuroprotective, gastroprotective, and antidiabetic. Our current study aims to shed light on the probable efficiency of ellagic acid in managing metabolic syndrome and its complications. Materials and methods: To prepare the present review, the databases or search engines utilized included Scopus, PubMed, Science Direct, and Google Scholar, and relevant articles have been gathered with no time limit until March 2023. Results: Several investigations indicated that ellagic acid could be a potent compound for the treatment of many disorders such as diabetes, hypertension, and hyperlipidemia by various mechanisms, including increasing insulin secretion, insulin receptor substrate protein 1 expression, regulating glucose transporter 4, triglyceride, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), attenuating tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), malondialdehyde (MDA), and oxidative stress in related tissues. Furthermore, ellagic acid ameliorates mitochondrial function, upregulates uncoupling protein 1 (found in brown and white adipose tissues), and regulates blood levels of nitrate/nitrite and vascular relaxations in response to acetylcholine and sodium nitroprusside. Conclusion: Ellagic acid can treat or manage metabolic syndrome and associated complications, according to earlier studies. To validate the beneficial effects of ellagic acid on metabolic syndrome, additional preclinical and clinical research is necessary.

Crocin's effect on phenotype switching of J774A.1 macrophages depends on their polarization state during exposure.

Objectives: Macrophages exhibit versatile phenotypes, with M1 macrophages releasing inflammatory cytokines and possessing microbicidal activities, while M2 macrophages release anti-inflammatory cytokines and contribute to tissue repair. The M1/M2 imbalance plays a significant role in various pathological processes. Crocin, known for its antioxidant properties and ability to eliminate free radicals, has been investigated for its potential anti-inflammatory effects. We examined the effect of the primary activation state of macrophages on their phenotype switching when exposed to crocin. Materials and Methods: The crocin impact on macrophage viability was evaluated by MTT. TNF-α, IL-6, and IL-10 secretion, as well as Nos2/Arg1 ratio, were measured in cells treated with crocin or LPS+IFN-γ (M1 inducers), in cells concurrently treated with crocin and LPS+IFN-γ or in cells pretreated with crocin before M1 induction. Results: Crocin did not show any toxicity at the concentration of 500 µM or lower. When uncommitted macrophages were exposed to crocin (25-100 µM), it elevated certain M1 activity indicators, including Nos2/Arg1 ratio and TNF-α secretion, but not IL-6. Crocin in concurrent treatment with LPS+IFN-γ prevented the increase in M1 indicators, Nos2/Arg1 ratio, and TNF-α secretion. However, pretreatment of cells with crocin before the addition of LPS+IFN-γ did not reverse M1 induction in macrophages; instead, it further increased the Nos2/Arg1 ratio and TNF-α secretion. IL-10 was not detectable in any of the experimental groups. Conclusion: It appears that the modulatory effects of crocin on macrophage M1/M2 phenotype switching partly depend on the presence or absence of inflammatory mediators and, accordingly, the initial state of macrophage commitment.