Immunomodulatory and antioxidant effects of hydroxytyrosol in cyclophosphamide-induced immunosuppressed broilers

Abstract

As an important olive component, hydroxytyrosol ( HT ) has good medicinal and health effects. However, its importance in alleviating immune suppression in broilers has not been established. Therefore, we aimed at evaluating the immunomodulatory and antioxidant effects of HT in immune suppressed broilers. Immune suppressed broiler models were established via intraperitoneal injection of 80 mg/kg cyclophosphamide ( Cy ). Thirty two Cobb 500 male broilers were randomly allocated into 4 groups of 8 each. Broilers in the model (Cy) and HT treatment (Cy+HT) groups were intraperitoneally administered with Cy (80 mg/kg BW) once a day for 3 d. From the 4th d, broilers in the Cy+HT and HT groups were treated with 0.5 mL of 200 mg/L HT solution, once a day, for 7 d. The Cy and Con groups were orally administered with normal saline. On the 14th and 28th d, serum and duodenal samples were obtained for testing. It was found that HT increased villi height ( VH )/crypt depth ( CD ) ratio in the duodenum and suppressed serum tumor necrosis factor-α ( TNF-α ) and interleukin-6 ( IL-6 ) levels. Moreover, it elevated the expressions of CD4+ and CD8+ T lymphocytes. HT upregulated the mRNA expression levels of interleukin-2 ( IL-2 ), interleukin-4 ( IL-4 ), and interleukin-10 ( IL-10 ), enhanced the activity of superoxide dismutase ( SOD ), glutathione peroxidase ( GSH-Px ), and downregulated malondialdehyde ( MDA ) levels in Cy-induced immune-suppressed broilers. In conclusion, HT can alleviate immune-suppression as well as enhance immunity and antioxidant activities in the local mucosa of small intestines in broilers. Therefore, it can be used as an immune stimulant. More studies should be performed to confirm our findings and to elucidate on the mechanisms of HT.

The Genus Alternanthera: Phytochemical and Ethnopharmacological Perspectives

“…Phytomolecules like Vitexin and vitexin analogs ( Rosa et al, 2016 ), Kaempferol and kaempferol analogs ( Lin et al, 2011 ; Swarnalatha et al, 2015 ), Quercetin and quercetin analogs ( Manjunath and Thimmulappa, 2021 ), Tricin ( Santos et al, 2017 ), Stigmasterol ( Antwi et al, 2017b ), β-Sitosterol ( Desai et al, 2009 ), Ferulic acid ( He F. et al, 2021 ), p-Coumaric acid ( Pragasam et al, 2012 ), and Chlorogenic acid ( Guo et al, 2021 ) which were previously reported from Alternanthera brasiliana (L.) Kuntze, may be responsible towards its immunomodulatory activity. Phytomolecules like Vitexin and vitexin analogs ( Rosa et al, 2016 ), Kaempferol ( Lin et al, 2011 ; Swarnalatha et al, 2015 ), Quercetin-3-methyl ether ( Martino et al, 2016 ), Quercetin and quercetin analogs ( Manjunath and Thimmulappa, 2021 ), Acacetin analogs ( Zhao et al, 2014 ), Stigmasterol ( Antwi et al, 2017b ), and Hydroxytyrosol ( Shan and Miao, 2022 ) which were previously reported from Alternanthera littoralis P.Beauv., may be responsible for its immunomodulatory activity.…”

Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine

“…In cyclophosphamide- and epirubicin-induced toxicity in Sprague–Dawley rats, four cycles of 150 mg/kg/week OLE reduced lipid peroxidation and increased the activity of antioxidant enzymes in heart, kidney, and liver [ 296 ]. Moreover, in a model of cyclophosphamide-induced immunosuppression in broilers, a solution containing 200 mg/L HT reduced duodenal MDA levels while increasing the activity of antioxidant enzymes [ 297 ]. In vitro, 50 μM and 70 μM HT reduced doxorubicin-mediated toxicity in embryonic rat cardiomyoblasts H9c2(2-1) after 48 h incubation.…”

“…Four cycles of 150 mg/kg/week OLE in Sprague–Dawley rats reduced serum TNF-α and IL-6 in an experimental model of epirubicin and cyclophosphamide toxicity [ 296 ]. In a model of cyclophosphamide-induced immunosuppression in broilers, a solution containing 200 mg/L HT promoted the duodenal expression of anti-inflammatory cytokines IL-4 and IL-10 [ 297 ].…”

Hydroxytyrosol mitigates Mycoplasma gallisepticum-induced pulmonary injury through downregulation of the NF-κB/NLRP3/IL-1β signaling pathway in chicken

“…HT suppresses the LPS-induced neuroinflammatory responses by modulating the microglial M1/M2 polarization and downregulating TLR-4 mediated NF-κB activation and ERK signaling pathway ( Zhang et al, 2020 ). Moreover, HT can reduce the immune suppression caused by Cy in chickens, increase the mRNA transcription levels of IL-2, IL-4, and IL-10, and inhibit the expression levels of inflammatory factors TNF-α and IL-6; therefore, it can be used as an immune enhancer in poultry farming ( Shan and Miao, 2022 ). A study further established an inflammatory model by stimulating mouse macrophages with LPS and reported that HT reduced the secretion of cytokines IL-1β and TNF-α; this clarified the molecular basis of HT in the treatment of inflammation ( Richard et al, 2011 ).…”