Organisms Commons^™

Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats, Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar

Pharmacy Faculty Articles and Research

The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, …

Attenuation Of Acute Rejection In A Rat Liver Transplantation Model By A Liver-Targeted Dextran Prodrug Of Methylprednisolone, Anjaneya Chimalakonda, Donald L. Montgomery, Jon A. Weidanz, Imam H. Shaik, Justin H. Nguyen, John J. Lemasters, Eiji Kobayashi, Reza Mehvar

Pharmacy Faculty Articles and Research

Background. The use of methylprednisolone (MP) and other corticosteroids for the treatment of acute liver allograft rejection is associated with severe toxicities in nontarget tissues. Therefore, selective delivery of NIP to the liver may improve its efficacy and alleviate its side effects. We investigated the effects of a novel liver-targeted dextran prodrug of MP (DMP) in an orthotopic rat liver transplantation (OLT) model.

Methods. The model consisted of a high responder rejection strain combination (Dark Agouti donors and Lewis recipients). Liver recipients were intravenously administered saline or a single subtherapeutic dose of MP (5 mg/kg) as the parent …