Protective roles of thymoquinone and vildagliptin in manganese-induced nephrotoxicity in adult albino rats.

Despite being important in the body's mechanisms, excessive accumulation of manganese (Mn) can induce severe toxicity in vital organs of the body. Thymoquinone (TQ) is extracted from Nigella sativa seeds which recently gained popularity as dietary supplements and plant-based antioxidants. Vildagliptin (VLD) is a dipeptidyl peptidase IV (DPPIV) inhibitor, approved as anti-hyperglycemic agents with cardioprotective and renoprotective effects. The present study aimed to investigate the nephrotoxicity of Mn and the potential protective effects of thymoquinone and vildagliptin. Sixty-four adult male albino rats were equally divided into 8 groups: group I (control, received no medication), group II (vehicle, received normal saline), group III (TQ, 50 mg/kg/day), group IV (VLD, 10 mg/kg/day), group V (MnCl2, 50 mg/kg/day), group VI (Mn+TQ), group VII (Mn+VLD), and group VIII (Mn+TQ+VLD). Groups VI, VII, and VIII, received the same previously mentioned doses. All drugs were orally gavaged for 12 weeks. Manganese administration resulted in an elevation in the levels of serum and tissues Mn, blood glucose, serum urea, creatinine, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and reduction in insulin, kidney superoxide dismutase (SOD), glutathione (GSH), and interleukin-10. Histopathological structural renal damage was detected associated with strong positive immunoexpression of caspase-3. On the other hand, individual or combined TQ and VLD administration with Mn significantly decreased the serum and tissue levels of Mn, declined the blood glucose, inflammatory markers, oxidative stress markers, ameliorated the histopathological effects, and down-regulated the immunoexpression of caspase-3. In conclusion, TQ and VLD co-administration elicited protective effects against Mn-induced nephrotoxicity.

Could aspartame exacerbate caffeine effects on renal maturation in rat's offspring? A biochemical and histological study.

BACKGROUND: Caffeine and aspartame (ASP) are mostly used as a diet regimen to reduce overweight. The risk increase if used during critical life periods that may affect the development of fetal organs. OBJECTIVE: To evaluate the individual and combined effects of maternal exposure to caffeine and ASP during gestation and lactation on the kidneys' development of rats' offspring. METHODS: Pregnant rats were divided randomly into four groups; Group I (control group). Group II (ASP group): ASP was given at a dose of 40 mg of /kg/day. Group III (Caffeine group): caffeine was given at a dose of 80 mg/kg/day. Group IV (ASP & caffeine group); where previous doses of ASP and caffeine were given at the same time. All the treatments were given by oral gavage from the first day of pregnancy until postnatal day 30. Kidneys of rats' offspring were dissected and tested for detection of oxidative stress markers and for histopathological & immunohistochemical examination. RESULTS: This study showed a high significant increase in oxidative load (malondialdehyde) in renal tissues in group IV associated with decreased activities of total glutathione and antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Histological and morphometric examination results showed delayed maturation of renal tissues in Group II and III, but more deleterious effects were observed in group IV with a lot of pathological changes in renal tissues. CONCLUSION: The extensive use of caffeine and ASP should be controlled to avoid the risk of their toxicity.

Magnetic resonance imaging of the proximal tibial epiphysis: could it be helpful in forensic age estimation?

There is an increasing demand for age estimations of living persons who are involved in civil and criminal procedures but lack a valid birth certificate indicating their date of birth. Several studies have recommended the application of magnetic resonance imaging (MRI) and assessment of the stage of epiphyseal fusion in age estimation. This study involved retrospective MRI analysis of 335 cases (217 males and 118 females) whose ages ranged from 8 to 28 years (yrs). We assessed the degree of ossification of the proximal tibial epiphysis depending on the classifications of Schmeling and Kellinghaus used for the main stages (I, II, III, IV & V) and substages (IIa, b, c & IIIa, b, c). Significant differences between males and females at stages IIIc, IV and V (p < 0.001) were observed. Additionally, the ossification of the proximal tibial epiphyses occurred earlier in females than in males (2-4 yrs). The mean of ages in stage IV was approximately 18.6 yrs. in females and 22.5 yrs. in males, meaning that stage IV can be used as a valuable forensic marker to determine whether the person in question has reached the age of 18 yrs. We concluded that the application of MRI in the assessment of the ossification status of the proximal tibial epiphysis could be helpful in age estimation for various forensic purposes.

Could curcumin ameliorate titanium dioxide nanoparticles effect on the heart? A histopathological, immunohistochemical, and genotoxic study.

The evaluation of the toxicological effects of titanium dioxide nanoparticles (TiO2NPs) is increasingly important due to their growing occupational and industrial use. Curcumin is a yellow curry spice with a long history of use in herbal medicine and has numerous protective potentials such as antioxidant, antimicrobial, anti-inflammatory, and anti-apoptotic effects. Accordingly, we tested the hypothesis that curcumin could ameliorate TiO2NP-induced cardiotoxic and genotoxic effects in adult male albino rats. For this purpose, 48 adult male albino rats were randomized into five groups; all treatment was by oral gavage once daily for 90 days: group I (8 rats), untreated control; group II (16 rats), subdivided into vehicle control IIa (8 rats) received saline and vehicle control IIb (8 rats) received corn oil; group III (8 rats) orally gavaged with curcumin dissolved in 0.5 ml corn oil at a dose of 200 mg/kg b.w./day; group IV treated with TiO2NPs at a dose of 1200 mg/kg b.w./day (1/10 LD50) suspended in 1 ml of 0.9% saline; group V treated with curcumin + TiO2NPs (the same previously mentioned doses). Curcumin was orally gavaged for 7 days before TiO2NPs treatment was initiated, and then they received TiO2NPs along with curcumin at the same doses for 90 days. TiO2NPs administration resulted in several myocardial cytomorphic changes as structurally disorganized, degenerated, and apoptotic cardiomyocytes and the newly implemented 3-nitrotyrosine immune expression rendered strong evidence that these effects derived from the cardio myocellular oxidative burden. Furthermore, comet assay results confirmed TiO2NP-related DNA damage. Remarkably, all these changes are partially mitigated in rats treated with both curcumin and TiO2NPs. Our results suggest that concurrent curcumin treatment has a beneficial role in ameliorating TiO2NP-induced cardiotoxicity and this may be mediated by its antioxidative property.

Alleviative effect of licorice on copper chloride-induced oxidative stress in the brain: biochemical, histopathological, immunohistochemical, and genotoxic study.

Although copper is an essential micronutrient involved in a variety of biological processes indispensable for sustaining life, it can be toxic when administered in excess. Licorice (Glycyrrhizaglabra) has been used in Chinese folk medicine for the treatment of various disorders. Licorice has the biological capabilities of detoxication, antioxidation, and antiinfection. Here, we test the hypothesis that licorice could ameliorate copper-induced neurotoxic and genotoxic effects in adult male albino rats. For this purpose, 48 adult male albino rats were randomized into five groups: group I (8 rats), untreated control; group II (16 rats), subdivided into; vehicle control IIa (8 rats) which received 1 mL saline twice weekly intraperitoneally for 8 weeks and vehicle control IIb (8 rats) received 0.5 mL distilled water/day orally gavaged for 8 weeks; group III (8 rats), treated with licorice dissolved in 0.5 mL of distilled water, 50 mg/kg b.w./day orally gavaged for 8 weeks; group IV (8 rats), copper chloride (CuCl2) dissolved in 0.5 mL saline, 7 mg/kg b.w. twice weekly intraperitoneal for 8 weeks; and group V (8 rats), CuCl2 + licorice (the same previously mentioned doses) licorice extract were orally given for 10 days before treatment was initiated then followed by CuCl2 intraperitoneally for 8 weeks. We found that CuCl2 exposure significantly increased brain oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content, and depressed antioxidant enzyme activities in brain tissues when compared with control groups. This was accompanied by histopathological changes in the form of increased cellularity and swelling of astrocytes that showed dense eosinophilic cytoplasm, pyknotic nuclei, and multiple apoptotic bodies that associated with degenerated neurons with deep eosinophilic cytoplasm. Also, strong Bax immunoreactions in the brain were detected. Furthermore, comet assay results confirmed CuCl2-related oxidative DNA damage. Notably, all these changes were partially ameliorated in rats treated concomitantly with licorice and CuCl2. Our results showed that licorice exerts protective effects against CuCl2-induced neuro- and genotoxicities. These effects may be attributed to the antioxidative property of licorice.

Efficacy of naringenin against permethrin-induced testicular toxicity in rats.

Permethrin (PM), a synthetic pyrethroid insecticide, has broad toxicity spectra. We aimed to investigate the effects of PM on the testes of adult albino rats, examine the recovery response and evaluate the efficacy of naringenin (NG) supplementation. Adult male albino rats were randomly assigned to five groups of six each: control, NG (50 mg/kg), PM (70 mg/kg), recovery (after subsequent withdrawal of PM) and NG-PM group. All treatments were given by oral gavage for 6 weeks and another 3 weeks for the recovery group. At the time of sacrifice, each testis was weighed. Biochemical analysis of epididymal sperm count and serum testosterone level was performed. Testes were processed for histological, ultrastructural and c-Kit immunohistochemical study. PM toxicity was evidenced by a highly significant decrease in testicular weight, epididymal sperm count and serum testosterone level compared to control. Furthermore, testicular structure abnormalities and reduced c-Kit immunoreactions were observed. Stoppage of PM in the recovery group partially reversed PM-induced changes. There was a mild decrease in testicular weight and biochemical parameters compared to control. The structure of seminiferous tubules was partially retained. The NG-PM group showed an overall improvement in testicular weight and biochemical alterations which were confirmed by light and electron microscopic examination. In conclusion, PM induced testicular toxicity, which was ameliorated by NG co-administration. However, stoppage of PM exposure was associated with partial recovery.

Alleviative effect of myricetin on ochratoxin A-induced oxidative stress in rat renal cortex: histological and biochemical study.

Ochratoxins (OTA) are secondary metabolites of Aspergillus and Penicillium. The detoxification of OTA has been of major interest due to its widespread threat to human health. We aimed to investigate the possible alleviative effect of myricetin (MYR) against OTA-induced damage in renal cortex of rats. Thirty adult male albino rats were randomized into five equal groups: control (untreated), vehicle control (0.5 ml corn oil/day including dimethylsulfoxide [DMSO]), MYR (100 mg MYR/kg b.w./day in distilled water), OTA (0.5 mg OTA/kg b.w./day; dissolved in 10% DMSO and then corn oil) and OTA + MYR group (received OTA and MYR at similar doses). All treatments were given by oral gavage for 2 weeks. At the end of the experiment, renal cortices were processed for light and electron microscope examinations. Immunohistochemical staining for localization of proliferating cell nuclear antigen (PCNA), p53 and transforming growth factor beta 1 (TGF-ß1) was carried out. Biochemical analysis of tissue glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress. OTA administration induced deleterious renal injury evidenced by the structural and ultra-structural changes. Immunohistochemical expression of p53, PCNA and TGF-ß1 were significantly up regulated compared with control. Alterations in antioxidant parameters supported that oxidative stress was one of the mechanisms involved in OTA toxicity. On the contrary, co-administration of MRY partially ameliorated OTA-induced renal injury. We suggest the potential effectiveness of MYR to counteract OTA-induced toxic oxidative stress on the renal cortex.