TBPH is a brominated flame retardant that exacerbates hepatic steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) mouse models. It disrupts phospholipid metabolism, reducing levels of cardiolipin (CL) and phosphatidylserine (PS). TBPH impairs endoplasmic reticulum-mitochondria (ER-Mito) contact, leading to mitochondrial dysfunction. Additionally, TBPH induces lung injury through a mitochondrial-derived ds-DNA mediated inflammatory response. It is also used to investigate the role of MFN2-mediated ER-Mito contact in lipid metabolism homeostasis.

TBPH (5-50 μM, 48 hours) accelerates the progression of NASH by disrupting MFN2-regulated ER-Mito contacts in the NASH LO model. In doses of TBPH (0-20 μg/mL, 48 hours), it reduces cell proliferation in TC-1 and BEAS-2B cells, induces oxidative stress, increases lung tissue fibrosis, leads to the release of ds-DNA from lung mitochondria, and activates c-GAS-STING.

TBPH, administered at 20-200 mg/kg via gavage once daily for 4 weeks, exacerbates hepatic lipid accumulation and metabolic dysfunction in an MCD diet-induced NASH mouse model. It accelerates liver inflammation and fibrosis, disrupts hepatic phospholipid homeostasis and ER-mitochondria contacts, inducing mitochondrial dysfunction and ER stress. In a normal diet (ND) mouse model, TBPH at the same dosage over 4 weeks does not alter liver morphology or liver-to-body weight ratio, but it impairs hepatocyte ER-mitochondria contact, leading to mitochondrial dysfunction and ER stress. Additionally, TBPH administered at 0-100 μg/mL via gavage daily for 4 weeks induces oxidative damage in lung cells of C57 mice and triggers inflammatory responses in lung cells and tissues.