The efficacy of platelet rich plasma as adjuvant therapy in the treatment of cryptosporidiosis in experimentally infected immunosuppressed rats

Abstract

Background: Cryptosporidium species are zoonotic opportunistic coccidian parasites that could cause disseminated life-threatening infection in the immunocompromised host. Unfortunately, few available drugs effectively eradicate the infectious oocyst with limited availability in developing countries. Although Nitazoxanide (NTZ) is the drug of choice for the treatment of cryptosporidiosis, it has limited efficacy in malnourished and immunocompromised patients. Moreover, platelet-rich plasma (PRP) successfully ameliorated the hepatic granuloma size in patients with parasitic schistosomiasis mansoni. Objective: This study aims to test the potential therapeutic effect of PRP versus the currently used NTZ, and/or using PRP as adjuvant therapy. Material and Methods: Sixty-five immunosuppressed rats were divided into 5 groups: non-infected as negative control (GI), infected non-treated as the positive control (GII), infected with Cryptosporidium spp. and treated with either intraperitoneal PRP (GIII), or NTZ (GIV), or a combination of intraperitoneal PRP and NTZ (GV). Parameters used for evaluation of the therapeutic efficacy included parasitological examination, histopathological examination of ileocaecal and liver specimens, and quantitative analysis of reduced glutathione (GSH) and malondialdehyde (MDA) for evaluation of oxidative stress markers, glutamic-oxaloacetic transaminase (SGOT), and glutamic pyruvic transaminase (SGPT) for evaluation of liver functions. Results: Parasitological and histopathological examinations revealed minimal improvement in GIII, marked improvement in GIV, and the best results were recorded in GV. The administration of PRP in GIII produced no significant changes in GSH, MDA, SGOT compared to positive control GII. Treatment with NTZ in GIV, and in addition to PRP in GV showed significant difference (P<0.05) compared to GII regarding serum results of GSH, MDA, and SGOT with the best results recorded in GV. GIV and GV showed reduction of serum levels of SGPT although there was statistically insignificant difference between the study groups. Conclusion: PRP could be used as a potential adjuvant therapy with NTZ to ameliorate the pathologic and inflammatory effects of cryptosporidiosis on the ileocaecal region. It also improves liver function in the immunocompromised hosts. Platelet-rich plasma in cryptosporidiosisEl-Kholy et al.,

Treatment of pyogenic liver abscess by surgical incision and drainage combined with platelet-rich plasma: A case report

“…Therefore, many PRP types have been used by clinicians for many years due to their advantageous effects on wound healing, cellular mitogenesis, osteogenesis, and angiogenesis[ 4 ]. PRP also exerts beneficial effects in terms of promoting tissue regeneration, mitigating infection due to the antibiotic-like action of the included leukocytes, and decreasing pain and blood loss[ 5 ].…”

“…PRP infusion causes notable liver regeneration in experimental animal models of liver dysfunction, as validated by a significant decrease in levels of liver enzymes (serum aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, and lactate dehydrogenase). PRP provides significant protection against liver fibrosis mainly via antifibrotic, antiapoptotic, and anti-inflammatory pathways[ 5 , 6 ]. Immediate contact between platelets and hepatocytes can evoke the release of soluble factors from platelets, such as IGF-1 and HGF, which are considered crucial mediators of liver recovery[ 7 ].…”

“…Oxidative stress is caused by a shift in the balance between oxidants and antioxidant cytokines and is caused by the overproduction of reactive oxygen species (ROS)[ 5 ]. A balance between ROS and the main antioxidant products (superoxide dismutase, catalase, and glutathione peroxidase) is needed to avoid damage from oxidative stress[ 5 ].…”

“…Oxidative stress is caused by a shift in the balance between oxidants and antioxidant cytokines and is caused by the overproduction of reactive oxygen species (ROS)[ 5 ]. A balance between ROS and the main antioxidant products (superoxide dismutase, catalase, and glutathione peroxidase) is needed to avoid damage from oxidative stress[ 5 ]. Partial hepatectomy causes liver injury and tissue loss due to an increase in ROS, which can lead to a reduction not only in cell growth but also in mitotic activity by inhibiting proteins of the cell cycle and disrupting DNA synthesis[ 9 - 11 ].…”

Anti-Cryptosporidial Drug-Discovery Challenges and Existing Therapeutic Avenues: A “One-Health” Concern

“…Therefore, Verbena officinalis (V. officinalis) was used to check its anti-cryptosporidial efficacy [106]. In immunosuppressed infected mice, V. officinalis and NTZ, when used in combination, showed novel results (87% efficacy), reducing the shed of oocysts in stools with minimum side effects [107]. Histopathological changes were minimal when this was used with the normal presence of goblet cells, and liver architecture was not disturbed (Table 2) [108].…”