Black Garlic and Thiosulfinate-Enriched Extracts as Adjuvants to Ceftriaxone Treatment in a Rat Peritonitis Model of Sepsis

Abstract

To date, there have been no new drugs or adjuvants able to decrease both morbidity and mortality in the context of sepsis and septic shock. Our objective was to evaluate the use of thiosulfinate-enriched Allium sativum and black garlic extracts as adjuvants in the management of sepsis. An experimental in vivo study was carried out with male Sprague–Dawley® rats. Animals were randomized in four treatment groups: antibiotic (ceftriaxone) treatment (group I), ceftriaxone plus thiosulfinate-enriched extract (TASE, group II), ceftriaxone plus thiosulfinate-enriched extract and black garlic extracts (TASE + BGE, group III), and ceftriaxone plus black garlic extract (BGE, group IV). All animals were housed and inoculated with 1 × 1010 CFU/15 mL of intraperitoneal Escherichia coli ATCC 25922. Subsequently, they received a daily treatment according to each group for 7 days. Clinical, analytical, microbiological, and histopathological parameters were evaluated. Statistically significant clinical improvement was observed in rats receiving garlic extracts in weight (groups II and III), ocular secretions, and piloerection (group IV). Moreover, less liver edema, vacuolization, and inflammation were observed in groups receiving adjuvant support (groups II, III, and IV). When comparing interleukins 24 h after bacteria inoculum, we found statistically significant differences in TNF-alpha levels in groups receiving BGE (groups III and IV, p ≤ 0.05). Blood and peritoneal liquid cultures were also analyzed, and we detected a certain level of Enterococcus faecalis in peritoneal cultures from all treatment groups and less bacteria presence in blood cultures in rats receiving garlic extracts (groups II, III, and IV). In conclusion, TASE and BGE could be promising nutraceutical or medicinal agents as coadjuvants in the treatment of sepsis because of its effects in modulating the inflammatory response.

Thiosulfinate-Enriched Allium sativum Extract Exhibits Differential Effects between Healthy and Sepsis Patients: The Implication of HIF-1α

“…In a previous study, using the same TASE as a adjuvant, we found TASE reduced inflammation in a rat peritonitis sepsis model [ 17 ]. We found different results when we evaluated the effects of TASE on the human monocyte response.…”

“…Allium sativum has traditionally been associated with beneficial effects in infectious processes due to its antimicrobial, anti-inflammatory, and antioxidant properties [ 6 , 17 , 31 , 32 ]. However, it has not yet been introduced in clinical settings.…”

“…However, it has not yet been introduced in clinical settings. Perhaps its most interesting application could be as an adjuvant to certain treatments [ 2 , 17 ]. In this regard, we and others have evaluated the potential use of garlic and its associated compounds in animal models of endotoxemia or sepsis, thereby revealing its protective effects [ 17 , 33 , 34 , 35 ].…”

“…In this regard, sepsis patients could benefit from the effects of garlic as this pathology is defined as a dysregulated inflammatory response against an infection. In a recent study, we found that thiosulfinate-enriched Allium sativum extract (TASE) used as an adjuvant to ceftriaxone treatment can improve weight and clinical signs (ocular secretions, piloerection) as well as reduce hepatic edema, vacuolization, and inflammation in a rat peritonitis model of sepsis [ 17 ]. Nevertheless, it should be noted animal models do not accurately reproduce the complexity of immune response observed in humans [ 18 , 19 ].…”