Modulation of the Sirtuin-1 signaling pathway in doxorubicin-induced nephrotoxicity (synergistic amelioration by resveratrol and pirfenidone).

The current study was conducted to determine the precise mechanisms of Sirtuin-1 (Sirt-1), TGF- ß (Transforming Growth Factor-ß), and long non-coding RNA Metastasis Associated Lung Adenocarcinoma Transcript 1 (LncRNA MALAT-1) in signaling pathways in doxorubicin (DOX)-induced nephrotoxicity. The potential therapeutic effect of Resveratrol and Pirfenidone in DOX toxicity was also assessed. Thirty-six male adult rats were evenly distributed into four groups: Group 1: control rats. Group 2: DOX exposed rats' group, each animal received 7.5 mg/kg DOX as a single intravenous dose, Group 3: DOX exposed group subjected to oral resveratrol (20 mg/kg/daily for two weeks), Group 4: DOX exposed group subjected to oral Pirfenidone (200 mg/kg once daily for 10 days). At the planned time, animals were sacrificed. Renal tissue was collected to assess matrix metalloproteinase-9 (MMP9), inflammatory and apoptotic markers: tumor necrosis factor-alpha (TNF- ß, caspase-3, cyclo-oxygenase-2 (COX-2), and oxidative stress markers: nitric oxide (NO), Glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD). Sirtuin-1 (Sirt-1), TGF-ß, and LncRNA MALAT-1 were quantitatively assessed by real-time RT-PCR in the whole blood. Results showed that the DOX group exhibited a significant increase in oxidative stress markers, and inflammatory, and apoptotic markers in the renal tissue. Histologically, the renal tubule lining cells exhibited vacuolar alterations in the cytoplasm, glomerular atrophy, and vascular congestion. Furthermore, renal degeneration was evident, as confirmed by the heightened immuno-expression of MMP9. Exposure to DOX resulted in a significant decrease in Sirtuin-1 (Sirt-1) with a significant increase in the TGFß, and LncRNA MALAT-1 gene expression. However, pre-treatment with either resveratrol/or Pirefenidone ameliorated the histological renal alterations, regulated the pathways of Sirt-1, TGFß, and LncRNA MALAT-1, and decreased all oxidative stress, inflammatory and apoptotic markers. In conclusion, DOX exposure leads to renal toxicity by inducing renal degeneration, oxidative stress, and apoptosis. Administration of either resveratrol or Pirfenidone counteracted these changes and protected the kidney against DOX-induced renal damage.

Heavy Metals Assessment and Health Risk to Consumers of Two Commercial Fish Species from Polyculture Fishponds in El-Sharkia and Kafr El-Sheikh, Egypt: Physiological and Biochemical Study.

Metal pollution is a major environmental concern worldwide, especially in Egypt. The aquaculture industry uses widespread artificial feeds to stimulate fish production, leading to metal accumulation in the aquatic environment. Heavy metal concentrations (HMCs) in sediments, water, and tissues were studied to study the effect of pollution levels on heamatological, and biochemical, immunological aspects of farmed fish as well as on human health. Results declared that the HMC levels in the water and sediment were significantly different between El-Sharkia and Kafr El-Sheikh fishponds (T-test, p < 0.05). This was supported by the metal pollution index in the water and sediment, indicating that El-Sharkia fishponds (ES fishponds) were more contaminated than Kafr El-Sheikh fishponds (KES fishponds). Also, HMCs in fish tissues were significantly increased in fish cultivated in ES fishponds than in KES fishponds. Haematological, immunological, and biochemical alterations of Bolti (Oreochromis niloticus) and Topara (Chelon ramada) fish were significantly different within the different fish species as well as the different fishponds. From the human health perspective, the THQ-HMC and HI-HMC associated with the consumption of muscle suggest a safe non-carcinogenic risk to human health. In contrast, cadmium poses a cancer risk to children who consume the muscular tissue of Bolti fish from ES fishponds, which should be regarded as a warning sign based on data indices and a human health perspective. In order to minimise HMC pollution in the aquaculture sector, it is advisable to take possible assessments and carry out continuous monitoring considering international WHO/FAO assessments.