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Growth inhibition and morphological changes caused by indomethacin in fibroblasts in vitro
Abstract:
In a definite range of concentrations indomethacin inhibits the multiplication of fibroblasts in vitro without influencing their viability. The effect of lethal doses of indomethacin on the fine structure of normal and transformed fibroblasts was investigated by light and electron microscopy. The cells grown in flat monolayers became roundish and, varying in sequence, small zeiotic blebs were bulging at the external cell membrane. Beside coarse vesicular transformation of the endoplasmatic reticulum and extension of the perinuclear spaces ballooning of the mitochondria occurred. After breaking up of the vesicles of the endoplasmatic reticulum loosening of the cytoplasmic ground substance associated with enlargement of the hyaline plasma margins was observed in further progress of the experiment. The internal structures of the mitochondria were completely disorganized. In the ultrastructure of the fibroblasts altered by lethal doses of indomethacin no specific sites of drug action could be identified.
Insights
Indomethacin halts fibroblast multiplication in vitro without affecting cell survival. Lethal doses cause significant cellular damage, including mitochondrial disorganization and membrane blebbing in fibroblasts.
Area of Science:
- Cell Biology
- Pharmacology
- Biochemistry
Background:
- Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) known for its anti-inflammatory and analgesic properties.
- Fibroblasts are crucial cells involved in wound healing and tissue repair.
- Understanding the cellular effects of indomethacin is important for its therapeutic applications and potential side effects.
Purpose of the Study:
- To investigate the effects of lethal doses of indomethacin on the fine structure of normal and transformed fibroblasts in vitro.
- To determine if specific sites of drug action could be identified at the ultrastructural level.
Main Methods:
- Light and electron microscopy were employed to examine fibroblast morphology.
- Fibroblasts were cultured in vitro and treated with varying concentrations of indomethacin.
Main Results:
- Indomethacin inhibited fibroblast multiplication in a concentration-dependent manner without affecting cell viability at sub-lethal doses.
- Lethal doses induced significant ultrastructural changes, including cell rounding, membrane blebbing, endoplasmic reticulum vesiculation, and mitochondrial disorganization.
- No specific sites of indomethacin action were identified within the fibroblast ultrastructure.
Conclusions:
- Indomethacin exerts cytotoxic effects on fibroblasts at lethal concentrations, leading to widespread cellular damage.
- The observed morphological changes suggest disruption of cellular integrity and organelle function.
- Further research is needed to elucidate the precise molecular mechanisms underlying indomethacin's cytotoxic effects on fibroblasts.