Dietary Green Tea Extract Prior to Spinal Cord Injury Prevents Hepatic Iron Overload but Does Not Improve Chronic Hepatic and Spinal Cord Pathology in Rats

Abstract

Spinal cord injury (SCI) disrupts autonomic regulation of visceral organs. As a result, a leading cause of mortality in the SCI population is metabolic dysfunction, and an organ central to metabolic control is the liver. Our recent work showed that rodent SCI promotes Kupffer cell (hepatic macrophage) activation, pro-inflammatory cytokine expression, and liver steatosis. These are symptoms of nonalcoholic steatohepatitis (NASH), the hepatic manifestation of metabolic syndrome, and these pre-clinical data replicate aspects of post-SCI human metabolic dysfunction. Because metabolic profile is highly dependent on lifestyle, including diet, it is likely that lifestyle choices prior to injury influence metabolic and hepatic outcomes after SCI. Therefore, in this study we tested if a diet rich in green tea extract (GTE), a known hepatoprotective agent, that began 3 weeks before SCI and was maintained after injury, reduced indices of liver pathology or metabolic dysfunction. GTE treatment significantly reduced post-SCI hepatic iron accumulation and blunted circulating glucose elevation compared with control-diet rats. However, GTE pre-treatment did not prevent Kupffer cell activation, hepatic lipid accumulation, increased serum alanine transaminase, or circulating non-esterified fatty acids, which were all significantly increased 6 weeks post-injury. Spinal cord pathology also was unchanged by GTE. Thus, dietary GTE prior to and after SCI had only a minor hepatoprotective effect. In general, for optimal health of SCI individuals, it will be important for future studies to evaluate how other lifestyle choices made before or after SCI positively or negatively impact systemic and intraspinal outcomes and the overall metabolic health of SCI individuals.

Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs Its Signaling Pathways in Liver and Adipose Tissue in Mice

“…Elevated serum triglycerides were observed at one month after SCI in T3-transected rats associated with increased visceral adiposity (72). In a separate study, serum FFA and glucose were elevated 42 days after a 200 kdyne contusion injury in rats (73). While extensive study of serum lipid profiles has been performed in patients with SCI (1), to date these studies have not characterized serum FFA levels.…”

“…Hepatic lipids, assessed by Oil red O staining, were also increased at 14 days post injury ( 11 ). A more recent study from the same group found elevated hepatic CD11b at 6-weeks after a 200 kdyne injury at T8 that was associated with increased mRNA levels for several cytokines, including TNFα and IL-1ß, and increased hepatocellular lipids and iron levels ( 73 ). These findings are in agreement with the increased expression of CD11b in liver in the current study.…”

Spinal Cord Injury Reduces Serum Levels of Fibroblast Growth Factor-21 and Impairs its Signaling Pathways in Liver and Adipose Tissue in Mice

“…Hepatic lipids, assessed by Oil red O staining, were also increased at 14 days post injury (11). A more recent study from the same group found elevated hepatic CD11b at 6-weeks after a 200 kdyne injury at T8 that was associated with increased mRNA levels for several cytokines, including TNFa and IL-1 β, and increased hepatocellular lipids and iron levels (73). These findings are in agreement with the increased expression of CD11b in liver in the current study.…”

Hyperbaric Oxygen Treatment Improves Intestinal Barrier Function After Spinal Cord Injury in Rats

“…Each rat was randomly assigned into three experimental groups: sham-operation group (SH), SCI group, or SCI+HBO group. Meanwhile, the experimental animals were also randomly assigned into four postoperative times (1,3,7, and 14 days). This study did not involve pathogenic microorganisms and was carried out in a general secondary laboratory, and all animals are specific pathogen free.…”

“…Apart from the disastrous sensory and motor losses following spinal cord injury (SCI), dysfunction of a variety of organ systems is also widely recognized, such as the gastrointestinal (GI) tract, lung, kidney, spleen, and liver (1,2). GI complications, e.g., barrier dysfunction, motility disorders, and microbial dysbiosis, reprehensively account for 11% of hospitalizations in SCI patients and are regarded as serious problems compromising quality of life (3,4).…”