Possible curative role of curcumin and silymarin against nephrotoxicity induced by gamma-rays in rats.

Curcumin (CUR) and silymarin (SLM) are powerful antioxidant and anti-inflammatory compounds with beneficial protective effects against renal diseases. The purpose of this study was to evaluate the efficacy of CUR and SLM alone or in combination on radiation (IR) induced kidney injury. The results showed that CUR and SLM alone or in combination attenuated the oxidative stress denoted by a reduction in the level of malondialdehyde (MDA), hydrogen peroxide (H2O2) and advanced oxidation protein products (AOPP) along with a marked increase of glutathione GSH content and total antioxidant capacity (TAC). Additionally, a significant decrease in the level of blood urea nitrogen (BUN), creatinine, Cystatin-C (CYT-C), neutrophil gelatinase-associated lipocalin (N-GAL) and Kidney Injury Molecule-1 (Kim-1) was recorded. Moreover, the treatment resulted in a remarkable decline in the serum levels of interleukin-18(IL-18), tumor necrosis factor- alpha (TNF-α), C reactive protein (CRP), BCL2 associated X protein (Bax), Factor-related Apoptosis (FAS) and the activity of Caspase-3 associated by an increase of B-cell CLL/lymphoma 2 (Bcl2) level. The results were confirmed with the histopathological examination. Kidney of irradiated showed glomerular atrophy, massive necrotic changes of expanded tubules with hyaline cast inside some tubules and apoptotic changes were recorded in some renal tubules. While irradiated rats treated with CUR and SLM exhibited marked preservation of the cellular structure of their kidney tissue. In conclusion, the combination of CUR and SLM could be more potent than a single agent on the biochemical and histological changes of the irradiated rat renal tissue.

Differential effect of Taraxacum officinale L. (dandelion) root extract on hepatic and testicular tissues of rats exposed to ionizing radiation.

Exposure to high doses of radiation negatively impacts on human organs. Dandelion (Taraxacum officinale ) L. has been used as a traditional folk. This study was to investigate the effect of dandelion root extract (DRE) on radiation -induced hepatic and testicular tissues injury. Animals were exposed to 8.5 Gy of gamma radiation applied as a shot dose and DRE (200 mg/kg/day), was orally supplemented to rats 14 days before and after irradiation. The results showed that DRE administration attenuated oxidative stress in the liver and testis denoted by a significant reduction in the level of MDA and PCO with a marked elevation in GSH and the activity of SOD, CAT and Gpx. Moreover, DRE administration showed positive modulation in the activity of PNPase, GLDH and GSH-Ts. Additionally, these alterations were associated with a significant decrease in the activity of ALT, AST, ALP, and LDH with a marked increase of AL level. Further, elevated levels of testosterone, LH and inhibin B, as well as StAR and P450scc gene expression and Zn level with a decrease of FSH level were noticed. Also, DRE reduced the level of IL-1ß, TNF-α, and caspase-3. Also administration of DRE significance diminished the histopathological changes in the hepatic and testicular tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes or fibrinoid necrosis of congested central vein and improving the seminiferous tubules and interstitial tissue between the tubules of the testis. In conclusion, treatment with DRE pre-irradiation is effective on both liver and testicular tissues of rats. Meanwhile, in the case of post-radiation administration, DRE was more effective on testicular tissue than liver. So we suggest that it is better to use the dandelion before exposure to radiation rather than after it.

Effect of Low-Dose Gamma Radiation and Lipoic Acid on High- Radiation-Dose Induced Rat Brain Injuries.

AIM: This work aims to investigate the possible radio-adaptive mechanisms induced by low-dose (LD) whole-body γ-irradiation alone or combined with alpha-lipoic acid (ALA) administration in modulating high-dose (HD) head irradiation-induced brain injury in rats. MATERIALS AND METHODS: Rats were irradiated with LD (.25 Gy) 24 hours prior HD (20 Gy), and subjected to ALA (100 mg/kg/day) 5 minutes after HD and continued for 10 days. At the end of the experiment, animals were sacrificed and brain samples were dissected for biochemical and histopathological examinations. RESULTS: HD irradiation-induced brain injury as manifested by elevation of oxidative stress, DNA damage, apoptotic, and inflammatory markers in brain tissue. Histological examination of brain sections showed marked alterations. However, LD alone or combined with ALA ameliorated the changes induced by HD. CONCLUSION: Under the present experimental conditions, LD whole-body irradiation exhibited neuroprotective activity against detrimental effects of a subsequent HD head irradiation. This effect might be due to the adaptive response induced by LD that activated the anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms in the affected animals making them able to cope with the subsequent high-dose exposure. However, the combined LD exposure and ALA supplementation produced a further modulating effect in the HD-irradiated rats.

A nano based approach to alleviate cisplatin induced nephrotoxicity.

BACKGROUND AND OBJECTIVE: Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated. METHODS: Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks. RESULTS: Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations. CONCLUSION: We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.

Effect of Low-Level Laser on Some Metals Related to Redox State and Histological Alterations in the Liver and Kidney of Irradiated Rats.

Low-level laser therapy (LLLT) is a type of medicine that uses laser light at low levels to activate the cellular chromophores and the initiation of cellular signaling. This study aimed to evaluate the photomodulation effect of LLL against ionizing radiation (IR)-induced metal disorders related to redox state in the liver and kidney of male rats. Rats were divided into 4 groups (control, LLLT, IR (7Gy), IR+LLLT). The results showed that LLLT 870 nm one time for 3 days post-irradiation revealed redistribution of iron (Fe), copper (Cu), zinc (Zn),calcium (Ca), magnesium (Mg), manganese (Mn), and selenium (Se) in the liver and kidney tissues. Moreover, LLLT attenuated the oxidative stress manifested by a marked reduction of hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE), total oxidant state (TOS), and oxidative stress index (OSI) associated with a significant increase in total antioxidant status (TAS), glutathione (GSH) content, and glutathione peroxide (GPx), glutathione reductase (GRx), superoxide dismutase(SOD), and catalase (CAT) activities. Moreover, LLLT displayed an increase in glutathione-S-transferase (GSH-T) and ceruloplasmin activities and a decrease in the activity of gamma-glutamyl transferase (γ-GT). Besides, LLLT significantly attenuated the histological changes in the liver and kidney tissues, denoted by a reduction in the necrotic and degenerative changes of hepatocytes and an improvement in the corpuscles and tubules of the kidney. In conclusion, LLLT could be used as an adjuvant treatment post-exposure to radiation, while it is not beneficial to use it on the normal tissue.