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1.
Life Sci ; 347: 122642, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38641047

RESUMO

Drug repurposing involves the investigation of existing drugs for new indications. It offers a great opportunity to quickly identify a new drug candidate at a lower cost than novel discovery and development. Despite the importance and potential role of drug repurposing, there is no specific definition that healthcare providers and the World Health Organization credit. Unfortunately, many similar and interchangeable concepts are being used in the literature, making it difficult to collect and analyze uniform data on repurposed drugs. This research was conducted based on understanding general criteria for drug repurposing, concentrating on liver diseases. Many drugs have been investigated for their effect on liver diseases even though they were originally approved (or on their way to being approved) for other diseases. Some of the hypotheses for drug repurposing were first captured from the literature and then processed further to test the hypothesis. Recently, with the revolution in bioinformatics techniques, scientists have started to use drug libraries and computer systems that can analyze hundreds of drugs to give a short list of candidates to be analyzed pharmacologically. However, this study revealed that drug repurposing is a potential aid that may help deal with liver diseases. It provides available or under-investigated drugs that could help treat hepatitis, liver cirrhosis, Wilson disease, liver cancer, and fatty liver. However, many further studies are needed to ensure the efficacy of these drugs on a large scale.


Assuntos
Reposicionamento de Medicamentos , Hepatopatias , Reposicionamento de Medicamentos/métodos , Humanos , Hepatopatias/tratamento farmacológico , Biologia Computacional/métodos , Descoberta de Drogas/métodos
2.
Life Sci ; 340: 122461, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38286208

RESUMO

Heavy metals are ubiquitous environmental toxicants that have been known to have a serious effect on human and animal health. Aluminum (Al) is a widely distributed metal in nature. Al exposure has a detrimental impact on human fertility. This review focused on Al-induced male reproductive toxicity and the potential therapeutic approaches with some phytochemicals. Data from the literature showed that Al exposure is accompanied by a drastic decline in blood levels of FSH, LH, and testosterone, reduced sperm count, and affected sperm quality. Al exposure at high levels can cause oxidative stress by increasing ROS and RNS production, mediated mainly by downregulating Nrf2 signaling. Moreover, several investigations demonstrated that Al exposure evoked inflammation, evidenced by increased TNF-α and IL-6 levels. Additionally, substantial evidence concluded the key role of apoptosis in Al-induced testicular toxicity mediated by upregulating caspase-3 and downregulating Bcl2 protein. The damaging effects of Al on mitochondrial bioenergetics are thought to be due to the excessive generation of free radicals. This review helps to clarify the main mechanism involved in Al-associated testicular intoxication and the treatment strategy to attenuate the notable harmful effects on the male reproductive system. It will encourage clinical efforts to target the pathway involved in Al-associated testicular intoxication.


Assuntos
Alumínio , Sêmen , Animais , Masculino , Humanos , Alumínio/toxicidade , Sêmen/metabolismo , Testículo , Estresse Oxidativo , Antioxidantes/farmacologia , Intoxicação por Metais Pesados/metabolismo , Reprodução , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/metabolismo
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