Vitamin A and Daucus carota root extract mitigate STZ-induced diabetic retinal degeneration in Wistar albino rats by modulating neurotransmission and downregulation of apoptotic pathways.

The objective of our study was to explore the deleterious effects of diabetes on the visual functions of the retina and to address whether the administration of vitamin A and carrot root extract (CE) confer retinal protection in hyperglycemic rats via modulation of oxidative stress, biochemical alternations, and retinal neurotransmission. Fifty male Wistar albino rats weighing 180 ± 12.41 g were randomized into five groups (n = 10): controls, diabetic group (injected with 40 mg/kg dissolved in 0.1 sodium citrate buffer), diabetic group treated with vitamin A (2,500 IU/kg, low dose), diabetic group treated with vitamin (5,000 IU/kg, high dose), and diabetic groups administered CE (200 mg/kg/every other day). Our findings showed that, compared to controls, diabetic rats showed a significant decrease in their retinal thickness, increased apoptotic ganglion cells, and a noticeable degeneration of their synaptic layers. The inner retina displayed increased activity of neovascularization; however, the outer retina exhibited vacuolar degeneration of the photoreceptor cell layer. Our biochemical assessments showed reduced levels of CAT, SOD, and GST along with increased lipid peroxidation. Concurrently, cellular angiogenic and stress markers were significantly elevated associated with increased apoptotic activities as evidenced by increased expressions of annexin-V and PARP. Furthermore, the neurotransmitter content of the retina was altered in diabetic rats compared to controls and diabetic-treated groups. Paradoxically, vitamin A and CE supplementation attenuate these retinal insults in diabetic animals and normalized aforementioned assayed parameters; evidencing that both treatments exerted ameliorative impacts and restored visual functions by diminishing oxidative stress and neuronal degeneration. PRACTICAL APPLICATIONS: Diabetes is a complex disease that involves various physiological perturbations especially visual functions. In our study, we showed that vitamin A and carrot root extract (CE) confer remarkable protection against retinal degeneration in STZ-induced diabetic rats. Our findings showed that the chemical and phytochemical ingredients of the vitamin A and CE substantially attenuated the histopathological changes, oxidative stress, inflammatory reactions, and cellular death in diabetic rats. These favorable changes are attributable to the high content of retinoic acid, carotenoids, and phenolic compounds that effectively regulates the production of visual pigments, increases the antioxidant defense system, and diminishes the pro-inflammatory and apoptotic pathways. Thus, the nutritional values of vitamin A and CE represent promising therapeutic choices to mitigate the retinal-induced diabetic insults.

Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats.

BACKGROUND: For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential of Nigella sativa derived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats. METHODS: The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis. RESULTS: The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent. CONCLUSION: Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.