RESUMO
Uterine fibroids (UF) represent an immense health burden throughout the world. Obesity is considered one of the risk factors for UF development; however, the underlying mechanisms remain largely unexplored. We investigated the effect of obesity on fibroblast activation and its association with inflammation, autophagy dysfunction, and oxidative stress in UF patients. Thirty-five pre-menopausal UF patients were included in this study and classified into non-obese group (BM1 ≤ 30 kg/m2, n = 15) and obese group (BMI > 30 kg/m2, n = 20). Tissue samples were collected from fibroids and adjacent normal myometrium. Our results showed increased expression of fibroblast activation protein (FAP) together with markers of autophagy, inflammation, and oxidative stress in UF patients, which were all more markedly upregulated in obese compared to non-obese patients. In addition, BMI was significantly positive correlated with FAP and autophagy markers. In conclusion, the results of the present study suggest that obesity-associated autophagy dysregulation together with increased FAP expression may increase the risk of UFs in obese women.
Assuntos
Autofagia , Endopeptidases/metabolismo , Leiomioma/complicações , Proteínas de Membrana/metabolismo , Obesidade/complicações , Estresse Oxidativo , Adulto , Feminino , Humanos , Leiomioma/metabolismo , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Miométrio/metabolismo , Obesidade/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: The present study was conducted to elucidate the underlying molecular mechanism as well as the potential hepatoprotective effects of royal jelly (RJ) against hepatic ischemia/ reperfusion (IR) injury. METHODS: Rats were assigned into four groups; sham (received vehicle), IR (30 minutes ischemia and 45 minutes reperfusion), sham pretreated with RJ (200 mg/kg P.O.), and IR pretreated with RJ (200 mg/kg P.O.). The experiment lasted for 28 days. RESULTS: Hepatic IR significantly induced hepatic dysfunctions, as manifested by elevation of serum transaminases, ALP and LDH levels. Moreover, hepatic IR caused a significant up-regulation of P38-MAPK, NF-κB-p65, TNF-α and MDA levels along with marked down-regulation of Nrf-2, HO-1, COX-4, cytoglobin, IκBa, IL-10, GSH, GST and SOD levels. Additionally, marked histopathological changes were observed after hepatic IR injury. On the contrary, pretreatment with RJ significantly improved hepatic functions along with the alleviation of histopathological changes. Moreover, RJ restored oxidant/antioxidant balance as well as hepatic expressions of Nrf- 2, HO-1, COX-4, and cytoglobin. Simultaneously, RJ significantly mitigated the inflammatory response by down-regulation of P38-MAPK, NF-κB-p65, TNF-α expression. CONCLUSION: The present results revealed that RJ has successfully protected the liver against hepatic IR injury through modulation of cytoglobin, Nrf-2/HO-1/COX-4, and P38-MAPK/NF-κB-p65/TNF- α signaling pathways.
Assuntos
Antioxidantes/química , Ácidos Graxos/química , Isquemia/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Citoglobina/genética , Citoglobina/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Ácidos Graxos/farmacologia , Feminino , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Hepatócitos , Humanos , Interleucina-10/metabolismo , Fígado , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Reperfusão , Transdução de Sinais , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND AND AIMS: Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. METHODS: 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. RESULTS: PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. CONCLUSIONS: Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.
