Induction of liver fibrosis by CCl4 mediates pathological alterations in the spleen and lymph nodes: The potential therapeutic role of propolis

Abstract

In an animal models, carbon tetrachloride (CCl 4 ) is a carcinogenic agent that causes liver fibrosis. The current study aims to investigate whether induction in liver-fibrosis by CCl 4 in the mouse model could promote the initiation of fibrosis in lymph node and spleen due to sustained increase of inflammatory signals and also aimed to clarify the protective therapeutic effects of propolis. The male mice (BALB/c) were categorized into three experimental sets and each group involved 15 mice. Control group falls into first group; group-II and group-III were injected with CCl 4 to induce liver-fibrosis and oral supplementation with propolis was provided in group-III for 4-weeks. A major improvement with hepatic collagen and α-smooth muscle actin (α-SMA) production was aligned with the activation of liver fibrosis from CCl 4 . Mice treated with CCl 4 exhibited collagen deposition towards liver sections, pathological alterations in spleen and lymph node architectures, and a significantly increase the circulation of both T&B cells in secondary lymphoid organs. Mechanically, the secondary lymphoid organs treated with CCl 4 in mice exposed a positive growth in α-SMA and collagen expression, increased in proinflammatory cytokine levels and a significant increase in TGF-β, NO and ROS levels. A manifest intensification in the expression of Nrf2, COX-2, and eNOS and upregulation of ASK1 and P38 phosphorylation. Interestingly, addition of propolis-treated CCl 4 mice, substantially suppressed deposition of liver collagen, repealed inflammatory signals and resorted CCl 4 -mediated alterations in signaling cascades, thereby repairing the architectures of the secondary lymphoid organs. Our findings revealed benefits of propolis against fibrotic complications and enhancing secondary lymphoid organ architecture.

Physiological and Immunological Study for the Effects of Onopordum Acanthium L. Seeds Oil in Male Rats Treated with CCL4

“…In this study, the toxicity of CCl4 in rats was manifested by an increase in the level of liver enzymes, serum lipids, TNF-α, CRP, WBC, ACE, urea and creatinine with decreased serum proteins, hemoglobin and FBW constituent with histopathological changes in the liver, kidney and spleen tissues. These results have been supported previously [6]. The detection of elevated level of serum aminotransferases is mostly indicated as abnormal liver function existing in the hepatic cells which indicates structural changes in the hepatic tissues and biliary system [27].…”

“…Chemicals that cause liver injuries are called hepatotoxins [3] such as CCl 4 that has been frequently used in experimental rodent animals for inducing liver damage [4]. It has been recently reported, that in addition to the liver, CCL 4 can induce damages in other organs such as the kidney and spleen [5][6]. However, this deterioration can be avoided naturally by some essential oils obtained from different plants [7].…”

Molecular Insights into the Antistress Potentials of Brazilian Green Propolis Extract and Its Constituent Artepillin C

“…Furthermore, secondary lymphoid organs showed a significant increase in the circulation of T and B cells as well as intracellular levels of TGF-β, Nrf2, COX-2, eNOS, ROS, NO, and proinflammatory cytokines. Propolis treatment caused substantial suppression of liver collagen deposition, inflammatory signaling cascades suggesting its benefits against fibrotic complications and cancer [ 46 ]. Cancer chemotherapy has been shown to induce cognitive dysfunction by induction of oxidative stress and neuroinflammation.…”

Bee gomogenat rescues lymphoid organs from degeneration by regulating the crosstalk between apoptosis and autophagy in streptozotocin-induced diabetic mice

“…Likewise, melatonin treatment protects lymphoid organs from diabetic effects (Ozkanlar et al 2016 ). Similarly, Sayed et al ( 2021 ) observed that propolis supplementation decreased collagenous fibers in the lymphoid organs of CCl4-treated animals.…”