Hey, nice find on the Lott, though I'm not sure I can stomach the recoil of that beast, personally. My very first suggestion, is go to accurate reloading's website. They are the ones that put out the funny videos of the guys shooting the 577 T rex. The forums there has a lot of info, but it caters to big bore guns, and African hunting. Lot of info on safaris, guides, laws, places to avoid, etc. Not to mention a wealth of info about the bigger guns. I'd say you're fine for the scope on the Lott, but if it does not have the leupold quick release mounts, the weaver style, then you may want that installed so that you can remove the scope easily and use iron sights. Some guys hate the safety on the cz550, and from what I read of it, I would too, and some convert it to the Winchester style safety. As you said, a lot of people like the CZ550, it's a big magnum action that can take the rigby and other monster rounds, and it has the heft. As long as it was bedded you should be ok, lots of complaints of cracked stocks from the Lott, if it's not bedded. Lot of guys brag about the 450gr Barnes bullet for the 458 win, and with the Lott, probably the 500gr barnes. There's numerous other loads too that get good reviews for penetration, expansion, and plain out stopping the nasties. Lot of Lott fans on accuratereloading.
Your 375, a lot of people like it as an all rounder, plains and the big stuff, but some like more power for the dangerous game. Remember, on the guided hunts you'll have a PH with a nasty charge stomper in case things go bad. The 550 is a tad heavy for a 375 as you said, so it wouldn't be my first choice either. I wouldn't consider the sendero either due to its heft. You might look at caliber requirements for where you plan to go for plains game, but a 300 mag, 338 caliber mag, or a lighter 375 would be ideal, barring restrictions on the 300 and 338. The scope on your 375 is a tad big IMO. I run a 2-7x on my 375H&H in a model 798. If you go for a new, lighter gun for plains game, you might use that 3.5-10x on it.
I have a 416 rem mag here, in a model 70. Just got it, and only have ran ten rounds thru it so far. I'm leaning towards a 1-6x VX-6 scope on it as of right now. Cape buffalo have my interest as well, and one of these days, if the world doesn't come to an end first, I'd like to travel over there and take one.