Table 3.

CYP3A Involvement in Pathological Processes.

The Relationship of Diseases and CYP3A		Diseases	CYP3A	Possible Mechanism of CYP3A Participation in Pathogenesis	Ref.
Diseases Related to the Participation of CYP3A Enzymes in Bile Acid Metabolism		Cholestasis at early stages	CYP3A4 induction	FXR and PXR pathways	[76,277]
		Cholestasis at later stages	CYP3A4 activity downregulation	Elevated levels of estrogen and bile acids in the blood	[74]
		Nonalcoholic fatty liver disease	CYP3A4 reduction of expression and function	Possible post-transcriptionally modulation miR-150-5p and miR-200a-3p	[140,290,291,292]
Diseases Associated with the Participation of CYP3A Enzymes in Arachidonic Acid Metabolism		Breast cancer	CYP3A4 overexpression	Stimulation of angiogenesis through the activation VEGF. Proliferation in cancer cell through the activation of PI3K—AKT and STAT3 pathways	[309,310,320]
		ER+HER2− breast cancer	CYP3A4 necessary for tumor formation	Suppression of autophagy, in part by inhibition of AMPK activation	[326]
		COVID-19	CYP3A activity	EETs production is catalyzed by CYP3A enzymes EETs play a role in kidney damage	[332]
Diseases Associated with the CYP3A Involvement in the Metabolism of Sex Steroids		Breast cancer	CYP3A4/3A5 overexpression	17-β-estradiol conversion to potentially genotoxic 16-α-hydroxyestrone. Expression is not associated with the presence of ER and progesterone receptor	[319,342,343]
		Ovarian cancer	CYP3A4, CYP3A5, CYP3A7, and CYP3A43 high protein levels	PXR–CYP3A pathway	[344]
		Prostate cancer	CYP3A5 mRNA and protein levels reduction		[346]
		Endometrial cancer	CYP3A4 expression enhancing	PXR–CYP3A pathway	[355,357]
Diseases Related to the Participation of CYP3A Enzymes in Vitamin D Metabolism		Vitamin D–dependent rickets	CYP3A4 increased activity	Inactivating effect of CYP3A4 on the active form of vitamin D. CYP3A4 I301T mutation.	[361,365,371] [375];
		Osteoporosis	CYP3A4 increased activity	Inactivating effect of CYP3A4 on the active form of vitamin D	[361,365,371]
		Breast cancer, Prostate cancer, Colorectal malignant tumors	CYP3A4 increased activity	Inactivating effect of CYP3A4 on the active form of Vitamin D. Vitamin D takes part in cancer cell proliferation by different ways.	[362,363,384,385,386]
		COVID-19	CYP3A activity	Vitamin D metabolism is catalyzed by CYP3A enzymes	[369]
				Vitamin D attenuates overexpression of inflammatory cytokines	[410]
Inflammation-Dependent Changes in the Expression and Activity of CYP3A Enzymes	Infections	Chronic hepatitis C	Low activity of CYP3A4	Possible CYP3A4 inhibition by IL-6	[396], [398,399].
		HIV	Low activity of CYP3A4		[396], [401]
		COVID-19	Low activity of CYP3A4	CYP3A4 inhibition by IL-6, and TNF	[403]
	Inflammatory Conditions	Type 2 diabetes mellitus	CYP3A suppression	CYP3A4 inhibition by IL-6 and TNF	[382,412]
		Rheumatoid arthritis	Suppression of CYP3A4-mediated metabolism	CYP3A4 inhibition by IL-1Ra, IL-6, and CXCL8	[413] [414] [415,416,417]
		Crohn‘s disease	Significant decrease in protein expression of CYP3A4 in the ileum and colon.		[421]
			Decrease mRNA CYP3A4 in inflamed small-intestinal tissue		[422]
			Significant decrease of CYP3A proteins in duodenum of children		[423]
		Celiac disease	Marked drop of CYP3A4 activity in vivo		[424]
			Downregulation of mRNA CYP3A4 in duodenum and ileum		[425]
	Cancer	Advanced ovarian cancer	Reduced CYP3A activity	CYP3A4 inhibition by IL-6, IL-8, and TNF	[427].
		Patients experiencing cancer progression	Significantly low CYP3A4 expression and activity	CYP3A4 inhibition by IL-6	[428,429]
Aberrant Intratumoral Expression of CYP3A Enzymes		Rhabdomyossarcoma	High expression of CYP3A4 and CYP3A5		[434]
		Ewing’s sarcoma metastasis	CYP3A4 overexpression		[436]
		Hepatocellu-lar carcinoma (HCC)	Aberrantly low CYP3A5 expression	CYP3A5 suppresses migration and invasion of HCC cells in vitro via inhibition of ROS–mTORC2–p-AKT signaling.	[438,439].
		Lung adenocarci-noma	CYP3A5 aberrantly underexpression	CYP3A5 significantly reduces the phosphorylation of a TGF-β signaling protein SMAD1, involved in cell growth, apoptosis, development, and immune responses.	[440]
		Prostate cancer	Intratumoral CYP3A5 activation	CYP3A5 mediates the growth of prostate cancer cells by facilitating nuclear translocation of AR.	[442,438]