Examining hepatoprotective effects of astaxanthin against methotrexate-induced hepatotoxicity in rats through modulation of Nrf2/HO-1 pathway genes.

Methotrexate (MTX), as a folic acid antagonist, is an effective drug in treating a wide range of malignancies and autoimmune diseases. However, the clinical use of MTX has been limited due to its side effects, the most common of which is hepatotoxicity. In this study, rats were randomly divided into six groups: three treatment groups received methotrexate and different doses of astaxanthin (AX) for 14 days. At the end of the study, blood samples were collected to determine serum levels of ALT, AST, ALP, and LDH. Also, liver tissues were isolated to evaluate antioxidant enzymes and markers of oxidative stress, histopathological damage, and expression of NF-E2-related transcription factor (Nrf2) and Heme oxygenase-1 (HO-1) genes. The results showed that administration of MTX significantly increased the levels of ALT, AST, ALP, and LDH in the blood, markers of oxidative stress, and histopathological damage in liver tissue and significantly reduced the levels of antioxidant enzymes and the expression of Nrf2 and HO-1 genes. On the other hand, treatment with AX decreased blood levels of ALT, AST, ALP, and LDH and oxidative stress markers and remarkably raises the activity of antioxidant enzymes and expression of Nrf2 and HO-1 genes in liver tissue. In addition, histopathological lesions were improved with AX administration. The findings of this study indicated that AX may be useful for the prevention of MTX-induced hepatotoxicity by improving oxidative and inflammatory changes.

Astaxanthin improves fatty acid dysregulation in diabetes by controlling the AMPK-SIRT1 pathway.

Due to the rising prevalence of metabolic disorders, including type 2 diabetes (T2DM), new prevention and treatment strategies are needed. The aim was to examine the effect of astaxanthin (AST) on the major regulatory metabolism pathway SIRT-MAPK and fatty acid (FA) profile of plasma in patients with T2DM. This clinical trial included 68 T2DM patients randomly assigned to receive 10 mg/day of oral AST (n = 34) or placebo (n = 33) for 12 weeks. The expression level of SIRT1, AMPK activity, and the level of fatty acids in the serum were examined. The results showed that AST could modify the serum levels of saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA), particularly that of Arachidonic acid, from 11.31±0.35 to 8.52±0.72 %. Also, AST increased the expression and activity levels of SIRT1 and AMPK, respectively. Pearson analysis also revealed a significant association between AMPK activity and Linoleic acid serum (LA) levels (~ -0.604, p~0.013). AST can modify the FA profile of plasma by inducing metabolizing cells to uptake them. Also, it can activate the SIRT-AMPK pathway related to metabolism regulation. See also Figure 1(Fig. 1).

Preparation and characterisation of a new form of silymarin as a potential antidiabetic agent in the adult male rat.

Silymarin is used for a wide variety of biological applications including, antidiabetic activities. However, the effectiveness of Silymarin is affected by its poor aqueous solubility and low systemic bioavailability after oral administration. The present study aimed to formulate a new, simple, and inexpensive form of silymarin solution. A new form of silymarin solution (NFSM) characterised by small particle size (227.5 nm), high entrapment efficiency (>82%), and appropriate zeta potential(-24.7mv). Moreover, the antidiabetic effects of NESM were evaluated relative to native Silymarin (SM). Oral administration of NFSM for 14 days in diabetic rats significantly decreased fasting blood glucose, oxidative stress levels, and improved lipid profile compared with SM. Also, NFSM significantly increased serum insulin levels, the gene expression of insulin and Pdx1, restored and improved the structure of the liver, and pancreas histologically. Our results concluded that NFSM may be an efficient carrier for oral delivery of silymarin for the management of diabetes and aggravated antioxidant status.

Curcumin supplementation prevents cisplatin-induced nephrotoxicity: a randomized, double-blinded, and placebo-controlled trial.

Background and purpose: Cisplatin-induced nephrotoxicity (CIN) remains the most prevailing unfavorable influence and may affect its clinical usage. This study sought to explore the possible impacts of curcumin on preventing CIN in human subjects. Clinical design: The investigation was a placebo-controlled, double-blinded, randomized clinical trial conducted on 82 patients receiving nano-curcumin (80 mg twice daily for five days) or an identical placebo with standard nephroprotective modalities against CIN. Data was gathered on patients' demographics, blood, urinary nitrogen, creatinine (Cr) levels, urinary electrolytes, and urine neutrophil gelatinase-associated lipocalin (NGAL) levels in treatment and placebo groups, 24 h and five days after initiating the administration of cisplatin. Findings/Results: Both investigation groups were alike considering the demographic characteristics and clinical baseline data. Curcumin administration led to a significant improvement in blood-urine nitrogen (BUN). BUN, Cr, glomerular filtration rate (GFR), and the ratio of NGAL-to-Cr considerably altered during the follow-up periods. However, the further alterations in other indices, including urinary sodium, potassium, magnesium, NGAL values, and potassium-to-Cr ratio were not statistically noteworthy. The significant differences in the NGAL-to-Cr ratio between the two groups may indicate the potential protective impact of curcumin supplementation against tubular toxicity. Curcumin management was safe and well-accepted; only insignificant gastrointestinal side effects were reported. Conclusion and implications: Curcumin supplementation may have the potential to alleviate CIN and urinary electrolyte wasting in cancer patients. Future research investigating the effects of a longer duration of follow-up, a larger participant pool, and a higher dosage of curcumin are recommended.

Antioxidant effects of astaxanthin and metformin combined therapy in type 2 diabetes mellitus patients: a randomized double-blind controlled clinical trial.

Background and purpose: Since the critical role of oxidative stress in the pathogenesis and complications of type 2 diabetes mellitus (T2DM) has been proven, antioxidant therapy is considered an applicable strategy to control T2DM development. This study aimed at evaluating the effect of astaxanthin (AST) supplementation combined with metformin on oxidative indices and antioxidant defenses in T2DM patients. Experimental approach: In this randomized, double-blind placebo-controlled trial, 50 T2DM subjects receiving metformin were supplemented with 10 mg/day AST or placebo for 12 weeks. Malondialdehyde concentration and serum total antioxidant capacity (TAC) were assessed as oxidative indices. We also evaluated NF-E2-related factor2 (Nrf2) as the most critical transcription factor of antioxidant defense. Moreover, the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase were calculated. Findings/Results: AST supplementation-metformin combination caused a significant increase in SOD and catalase activities, as well as inducing Nrf2 protein expression compared to the placebo group. Significant changes in serum malondialdehyde and TAC between the AST group and placebo group after supplementation were not observed, although a significant increase was observed in TAC within the AST group after supplementation (32.67 ± 6.73) to before (25.86 ± 5.98). These results remained without change after adjustment for potential confounders. Conclusion and implications: Our study demonstrated that AST supplementation controlled oxidative stress through a synergistic effect with metformin and ameliorated overall antioxidant capacity by inducing Nrf2 transcription factor and activating SOD and catalase in T2DM patients. As a result, AST and metformin combination therapy can be considered beneficial in modifying oxidative stress and preventing T2DM complications.