The experimental uveitis was induced by injecting lens protein into the antertor cham- ber of rabbit's eye.A special fluorophotometer was used for objectively measuring the flaoreseein level in the anterior chambe...The experimental uveitis was induced by injecting lens protein into the antertor cham- ber of rabbit's eye.A special fluorophotometer was used for objectively measuring the flaoreseein level in the anterior chamber of the eve to rellect the degree of inflammation.When administered in- travenously.the inhibitory effects of flufenamic acid and mefenamic acid on experimental uveius showed a dose-dependent relationship,The former at dosages 5.0.12.5 and 250 mg kg decreased the areas under the time-response curve to 22.3%.11.5% and 9.3% of the control.respcctively:however the latter at dosages 6.2.12.5 and 25.0 mg/kg decreased the areas under the curve to 35.5%.21.0% and 8.6% of the control,respectively.When instilled by ocular route.50μl of 1% eye-drops of flufenmic acid or mefenamic acid lowered the fluoreseein levels of treated eyes as well as contra-lateral eyes.The areas under the time-response curve for treated eyes were decreased to 20.3% of the control and those of contra-lateral eyes to about 50% of the control.The results indicate that both flufenamic and mefenamic acids,applied intravenously or topically,can inhibit ocular inflammation.展开更多
The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating m...The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.展开更多
文摘The experimental uveitis was induced by injecting lens protein into the antertor cham- ber of rabbit's eye.A special fluorophotometer was used for objectively measuring the flaoreseein level in the anterior chamber of the eve to rellect the degree of inflammation.When administered in- travenously.the inhibitory effects of flufenamic acid and mefenamic acid on experimental uveius showed a dose-dependent relationship,The former at dosages 5.0.12.5 and 250 mg kg decreased the areas under the time-response curve to 22.3%.11.5% and 9.3% of the control.respcctively:however the latter at dosages 6.2.12.5 and 25.0 mg/kg decreased the areas under the curve to 35.5%.21.0% and 8.6% of the control,respectively.When instilled by ocular route.50μl of 1% eye-drops of flufenmic acid or mefenamic acid lowered the fluoreseein levels of treated eyes as well as contra-lateral eyes.The areas under the time-response curve for treated eyes were decreased to 20.3% of the control and those of contra-lateral eyes to about 50% of the control.The results indicate that both flufenamic and mefenamic acids,applied intravenously or topically,can inhibit ocular inflammation.
基金funded by Coordination for the Improvement of Higher Education Personnel (CAPES,Brazil-Finance Code 001,to LRB)the S?o Paulo Research Foundation(FAPESP,Brazil,project#2018/07366-4)+1 种基金The National Council for Scientific and Technological Development (CNPq,Brazil,project#303006/2018-8,to LRB)a PhD fellowship from FAPESP under Grant Agreement No 2020/02109-3。
文摘The transient receptor potential melastatin 2 is a calcium-permeable cation channel member of the TRP family. Also known as an oxidative stress-activated channel, the transient receptor potential melastatin 2 gating mechanism is dependent on reactive oxygen species. In pathological conditions, transient receptor potential melastatin 2 is overactivated, leading to a Ca~(2+) influx that alters cell homeostasis and promotes cell death. The role of transient receptor potential melastatin 2 in neurodegenerative diseases, including Alzheimer's disease and ischemia, has already been described and reviewed. However, data on transient receptor potential melastatin 2 involvement in Parkinson's disease pathology has emerged only in recent years and the issue lacks review studies that focus specifically on this topic. The present review aims to elucidate the role of the transient receptor potential melastatin 2 channel in Parkinson's disease by reviewing, summarizing, and discussing the in vitro, in vivo, and human studies published until August 2022. Here we describe fourteen studies that evaluated the transient receptor potential melastatin 2 channel in Parkinson's disease. The Parkinson's disease model used, transient receptor potential melastatin 2 antagonist and genetic approaches, and the main outcomes reported were discussed. The studies described transient receptor potential melastatin 2 activation and enhanced expression in different Parkinson's disease models. They also evidenced protective and restorative effects when using transient receptor potential melastatin 2 antagonists, knockout, or silencing. This review provides a literature overview and suggests where there is a need for more research. As a perspective point, this review shows evidence that supports transient receptor potential melastatin 2 as a pharmacological target for Parkinson's disease in the future.
