Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Ameliorative impacts of astaxanthin against atrazine-induced renal toxicity through the modulation of ionic homeostasis and Nrf2 signaling pathways in mice.

Astaxanthin (ASX), a red pigment belonging to carotenoids, has antioxidant activity and anti-oxidative stress effect. Atrazine (ATZ), a frequently used herbicide, whose degradation products are the cause for nephrosis and other oxidative stress associated diseases. This study was aimed to reveal the potential protective mechanism of astaxanthin against atrazine-induced nephrosis. Atrazine was orally given (250 mg/kg bw) to the mice along with astaxanthin (100 mg/kg bw) for 28 days. Serum biochemical indicators, oxidative stress biomarkers, ATPase activities, ion concentration, histomorphology, and various renal genes expression linked with apoptosis, Nrf2 signaling pathway, and aquaporins (AQPs) were assessed. It was found that serum creatinine (SCr), blood urea nitrogen (BUN), and MDA levels were significantly increased after the treatment of atrazine, whereas serum renal oxidative stress indicators like CAT, GSH, T-AOC, SOD decreased. Renal histopathology showed that atrazine significantly damaged renal tissues. The activities of Ca 2+-Mg 2+-ATPase were increased whereas Na +-K +-ATPase decreased significantly (P < 0.05). Moreover, results confirmed that the expression of AQPs, Nrf2, and apoptosis genes were also altered after atrazine administration. Interestingly, astaxanthin supplementation significantly (P < 0.05) improved atrazine-induced nephrotoxicity via decreasing SCr, BUN, oxidative stress, ionic homeostasis and reversing the changes in AQPs, Nrf2, and apoptosis gene expression. These findings collectively suggested that astaxanthin has strong potential ameliorative impact against atrazine induced nephrotoxicity.

Ameliorative impacts of sinapic acid against mercuric chloride-induced renal toxicity: role of antioxidants and inflammatory cytokines.

Because of their beneficial properties, natural products, especially medicinal plants, are becoming increasingly popular worldwide and play a significant role in research. This study was aimed to evaluate the nephroprotective effect of sinapic acid against mercuric chloride-induced renal toxicity in mice. The mice were allocated to four groups named a normal group (G1), model group (G2; received HgCl2, 1 mg/kg bw), treatments groups (G3 and G4: received 50 and 100 mg/kg bw of sinapic acid together with HgCl2). Mice received HgCl2 remarkably showed alteration in all examined biochemical biomarkers (urea, creatinine, and bilirubin), and induced alteration in blood cell picture and anemia. HgCl2 intoxication decreased both systemic and renal antioxidant activity and induced over all oxidative stress as indicated by alteration in inflammation and oxidative stress associated markers. HgCl2 affected renal histology with leukocytic and inflammatory cell infiltration, fibrosis and tubular necrosis. Administration of sinapic acid (50 and 100 mg/kg bw) markedly restored the HgCl2-induced oxidative stress (serum and renal: MDA, GSH, CAT, SOD, and T-AOC), proinflammatory cytokines (serum and renal: TNF-α, IL-6, IL-1ß, and PGE2) and restored the changes on biochemical markers, and hematological parameters (hemoglobin, erythrocytes, platelets, and leukocytes). Taken together, the results of the present study disclose that sinapic acid has the potential to attenuate HgCl2-induced renal toxicity and may be an ideal choice against mercury poisoning.

Screening impacts of Tilmicosin-induced hepatic and renal toxicity in rats: protection by Rhodiola rosea extract through the involvement of oxidative stress, antioxidants, and inflammatory cytokines biomarkers.

Tilmicosin (TIL) is a semisynthetic macrolide antibiotic with a broad spectrum of activity derived from tylosin. TIL is effective in the treatment of bovine and ovine respiratory diseases caused by different microbes. In parallel, Rhodiola rosea (RHO) is a popular herbal remedy because of its anti-inflammatory and antioxidant qualities. The experiment lasted for 12 days. Depending on the experimental group, the animals received either distilled water or RHO root extract dissolved in distilled water for 12 days through a stomach tube, and the single subcutaneous injection on day 6 of the experiment of either 500 µL of 0.9% NaCl or TIL dissolved in 500 µL 0.9% NaCl. Samples and blood were collected for serum analysis, gene expression, and immunohistochemistry screening at liver and kidney levels. TIL injection increased serum levels of hepatic and renal markers (ALP, ALT, AST, TC, TG, creatinine, and urea) with decreased total proteins. In parallel, TIL induced hepatic and renal oxidative stress as there was an increase in malondialdehyde levels, with a decrease in catalase and reduced glutathione activities. Of interest, pre-administration of RHO inhibited TIL-induced increase in hepato-renal markers, decreased oxidative stress, and increased liver and kidney antioxidant activities. Quantitative RT-PCR showed that TIL increased the liver's HSP70 (heat shock protein), NFkB, and TNF-α mRNA expression. Moreover, TIL upregulated the expression of desmin, nestin, and vimentin expression in the kidney. The upregulated genes were decreased significantly in the protective group that received RHO. Serum inflammatory cytokines and genes of inflammatory markers were affected in liver tissues (HSP70, NFkB, and TNF-α) and kidney tissues (desmin, nestin, and vimentin)-TIL-induced hepatic vacuolation and congestion together with glomerular atrophy. The immunoreactivity of PCNA and HMGB1 was examined immunohistochemically. At cellular levels, PCNA was decreased while HMGB1 immunoreactivity was increased in TIL-injected rats, which was improved by pre-administration of RHO. RHO administration protected the altered changes in liver and renal histology. Current findings support the possible use of RHO to shield the liver and kidney from the negative effects of tilmicosin.

Hepatoprotective Effect of Moringa Oil on Rats under Fungicide Toxicity.

The present study is designed to evaluate whether pretreatment with moringa would have a protective effect on thioacetamide (TAA)-induced liver fibrosis, assessing biochemical and histopathological changes in Wistar male rats. Exposure to TAA induced notable biochemical and histopathological alterations. Liver fibrosis induced by TAA, along with associated biochemical and histological damage, has not been previously investigated in male rats supplemented with moringa oil. The experiment involved forty male rats distributed across four groups, each comprising ten rats. Group 1 served as controls and received intraperitoneal injections of saline solution twice weekly for six weeks. Group 2 rats were injected with 300 mg/kg body weight of TAA (Sigma-Aldrich Corp.) twice weekly for the same duration. Group 3 rats were orally supplemented with moringa oil at 800 mg/kg body weight/day and received intraperitoneal injections of TAA at the same dosage as Group 2 for six weeks. Finally, Group 4 rats were injected with saline solution twice weekly and orally supplemented with moringa oil at 800 mg/kg body weight/day for the same period. At the end of the experiment, we determined body weight and performed liver function analysis. Additionally, we examined the liver histology of the different groups. Results showed that moringa oil treatment protected rat livers from TAA toxicity by improving liver function analysis and preventing liver fibrosis. Moringa oil can be considered a promising agent for protection against TAA toxicity.

The Efficacy of Dose Increments of Botulinum Toxin A in the Treatment of Childhood Esotropia.

BACKGROUND: Botulinum toxin is known to have a powerful chemodenervation effect, and it is a well-established alternative to incisional surgery for strabismus. This study aims to investigate the efficacy of dose increments of botulinum toxin A (BTA) for the treatment of specific ranges of angle deviation. METHODS: This was a prospective study that included patients presenting with esotropia to Dhahran Eye Specialist Hospital between 2016 and 2020, who were managed by a single surgeon. Botulinum toxin was given in different dosages (2.5, 5, 7.5, 10 international units (IU)) according to the size of deviation (11-19, 20-29, 30-39, and ≥40 prism diopters (PD)), respectively. A successful outcome was defined as deviation ≤10 PD in the last visit (a minimum of 6 months) following a single injection. RESULTS: A total of 56 patients with esotropia were included. The mean pre-treatment angle of deviation was 38.6 ± 2.5 PD. BTA injection in a dose of 2.5 IU for the 11-19 PD angle of deviation showed the highest rate of successful outcomes (75%). According to the type of esotropia, partially accommodative esotropia showed the best response to the use of dose increments (59%). The incidence of ptosis post-BTA injection was the least (37.5%) with the smallest dose (2.5 IU). CONCLUSION: BTA usage in dose increments is safe, efficient, and might be more cost-effective with less incidence of BTA associated complications. Different esotropia diagnoses have different clinical responses. However, larger studies are necessary to better predict the outcome of using dose increments.