RESUMO
Aluminum oxide nanoparticles (Al2O3 NPs) are among the most extensively utilized nanoparticles in nanotechnology and that have negative impacts on the environment. Therefore, the intention of this work is to investigate the protective and therapeutic effects of curcumin in nanoform (Cur NPs) against Al2O3 NPs induced kidney toxicity, oxidative stress, DNA damage, and changes in necrosis factor alpha (TNFα) and proliferating cell nuclear antigen (PCNA) expressions in male rats. Fifty healthy adult male were divided into five groups [G1, control; G2, received 50 mg/kg/day for 4 weeks of Cur NPs orally; G3, received 6 mg/kg BW orally for 4 weeks of Al2O3 NPs; G4, (Cur NPs + Al2O3 NPs) received Cur NPs and Al2O3 NPs at a dose similar to G2 and G3, respectively for 4 weeks; G5, (Al2O3 NPs + Cur NPs) received Al2O3 NPs at a dose similar to G3 for 4 weeks then received Cur NPs at a dose similar to G2 for another 4 weeks]. Current results revealed that Al2O3 NPs induced a significant elevation in serum urea, creatinine, chloride, calcium, kidney malondialdehyde (MDA), DNA damage, injury, TNFα and PCNA expressions and a significant depletion in serum potassium, kidney superoxide dismutase (SOD), glutathione (GSH) as compared to control. On the other hand, treatments of Al2O3 NPs with Cur NPs induced modulation in all altered parameters and improved kidney functions and structure, with best results for the Al2O3 NPs + Cur NPs than Cur NPs + Al2O3 NPs. In conclusion, Cur NPs has the capacity to mitigate the renal toxicity induced by Al2O3 NPs in male albino rats.
Assuntos
Óxido de Alumínio , Curcumina , Dano ao DNA , Rim , Estresse Oxidativo , Antígeno Nuclear de Célula em Proliferação , Fator de Necrose Tumoral alfa , Animais , Masculino , Estresse Oxidativo/efeitos dos fármacos , Curcumina/farmacologia , Dano ao DNA/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Óxido de Alumínio/toxicidade , Ratos , Nanopartículas/toxicidade , Nanopartículas/química , Ratos Wistar , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/químicaRESUMO
Neocryptolepine (5-methyl-5H-indolo[2,3-b] quinoline) analogs were synthesized and evaluated in vitro and in vivo for their effect versus Ehrlich ascites carcinoma (EAC). The analogs showed stronger cytotoxic activity against EAC cells than the reference drug. The in vivo evaluation of the target compounds against EAC-induced solid tumor in the female albino Swiss mice revealed a remarkable decrease in the tumor volume (TV) and hepatic lipid peroxidation. A noticeable increase of both superoxide dismutase (SOD) and catalase (CAT) levels was reported (p < 0.001), which set-forth proof of their antioxidant effect. In addition, the in vitro antioxidant activity of the neocryptolepine analogs was screened out using the DPPH method and showed promising activities activity. The histopathological investigations affirmed that the tested analogs have a remarkable curative effect on solid tumors with minimal side-effect on the liver. The study also includes illustrated mechanism of the antitumor activity at the cell level by flow cytometry. The cell cycle analysis showed that the neocryptolepine analogs extensively increase the aggregation of tumor cells in three phases of the cell cycle (G0/G1, S and G2/M) with the emergence of a hypo-diploid DNA content peak (sub-G1) in the cell cycle experiments, which is a clear-cut for the apoptotic cell population. Furthermore, the immunological study manifested a significant elevation in splenic lymphocyte count (p < 0.001) with the elevation of the responsiveness of lymphocytes to phytohemagglutinin (PHA). These results indicate that these naturally-based neocryptolepine alkaloids exhibit marked antitumor activity in vivo and represent an important lead in the development of natural-based anticancer drugs.
Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Produtos Biológicos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Indóis/farmacologia , Quinolinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Carcinoma de Ehrlich/enzimologia , Carcinoma de Ehrlich/patologia , Catalase/antagonistas & inibidores , Feminino , Técnicas In Vitro , Indóis/química , Camundongos , Quinolinas/química , Superóxido Dismutase/antagonistas & inibidores , Inibidores da Topoisomerase II/farmacologia , Células Tumorais CultivadasRESUMO
Cancer is the most serious disorder that may affect a person and is also the leading cause of mortality. Worldwide, breast cancer continues to be the leading cause of cancer-related deaths in women. The popularity of treating diseases using alternative and complementary medicines has increased in recent decades; many of these are derived from plants. Chamomile has a beneficial effect in treating many diseases, there for the purpose of this work is to study how chamomile protect against cardiac damage and toxicity brought on by Ehrlich solid tumor (EST) in adult female mice. 40 female mice were distributed in 4 groups (control, chamomile, EST, EST+chamomile). The research results indicated that EST caused significant alterations in cardiac function and structure. EST induced a significant elevation in serum creatine kinase (CK), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and myoglobin (MB), potassium, chloride ions, cholesterol, triglycerides, low-density lipoprotein (LDL), cardiac tissue damage, apoptotic P53 and Caspase 3 expressions while levels of sodium ions and high-density lipoprotein (HDL) were significantly decreased. Treatments of EST with chamomile improved the biochemical, histopathological, and Immunohistochemical alterations. This suggests that chamomile may be useful as an adjuvant for the treatment and prevention of cardiac toxicity.